NIH_SPENDING_CATS: Biomedical Imaging;Cancer

ORG_CITY: MADISON

ORG_DEPT: PHYSICS

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Project Narrative: This training program prepares advanced predoctoral students and postdoctoral trainees in the radiological sciences of cancer research and treatment with the skills needed to advance their careers and their science. Researchers in this field continue to have a high impact on the diagnosis and treatment of cancer, leading to major advances particularly in the areas of medical imaging, image guided intervention and radiation therapy.

PI_NAMEs: BEDNARZ, BRYAN PATRICK (contact)

PROGRAM_OFFICER_NAME: BOULANGER-ESPEUT, CORINNE A

PROJECT_TITLE: UW Radiological Sciences Training Program


ADMINISTERING_IC: HL

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular

ORG_CITY: HOUSTON

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PHYSIOLOGY

ORG_FIPS: US

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: PROJECT NARRATIVE The goal of the ‘Cardiovascular Research and Drug Development’ (CRDD) training program at Baylor College of Medicine is to educate and train the next generation of leaders in the field of cardiovascular research and drug discovery. Our innovative program includes interactive didactic courses, individualized training plans, formal training of research mentors, mentor training of the predoctoral trainees, and an exceptional research infrastructure within the largest medical center in the world. The program emphasizes the highest standards of rigor and reproducibility, equity, and ethics, while incorporating strong translational components to allow our trainees to bridge critically important gaps in basic and translational cardiovascular research to develop future therapeutic interventions.

PI_NAMEs: WEHRENS, XANDER H.T. (contact);YOUNG, DAMIAN WINSTON

PROGRAM_OFFICER_NAME: HUANG, LI-SHIN

PROJECT_TERMS: Cardiovascular system;drug development;research and development;Training Programs

PROJECT_TITLE: Cardiovascular Research and Drug Development (CRDD) training program

STUDY_SECTION: NITM

STUDY_SECTION_NAME: NHLBI Institutional Training Mechanism Study Section[NITM (JA)]


ADMINISTERING_IC: GM

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Clinical Research;Neurosciences

ORG_CITY: ANN ARBOR

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE  Improving short-term mortality and long-term morbidity from critical illness is a crucial public health priority. Glucocorticoid stress hormones play important roles in these short and long-term outcomes. This research program focuses on improving our understanding of glucocorticoid mechanisms of short- and long-term critical illness outcomes with the ultimate goal of maximizing their therapeutic potential.

PI_NAMEs: SPENCER-SEGAL, JOANNA LOUISE (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Acute;Area;Biological;Brain Stem;Cardiovascular system;Collaborations;Critical Care;Critical Illness;Endocrinology;Environment;Funding;Glucocorticoid Receptor;Glucocorticoids;Goals;Health Care Costs;Homeostasis;Hormones;Hospitals;Hypotensives;Immune;improved;industry partner;Inflammatory;laboratory experience;Maintenance;Memory;Mental Health;Mentors;Morbidity - disease rate;mortality;multidisciplinary;neural circuit;Neurosciences;next generation;novel;novel strategies;Outcome;Peripheral;Physicians;Play;Population;Positioning Attribute;programs;public health priorities;Research;Resistance;response;Role;Running;Scientist;Sepsis;Signal Transduction;skills;Stress;Survivors;Testing;Therapeutic;tool;translational research program;Work

PROJECT_TITLE: Glucocorticoids in short- and long-term critical illness outcomes

STUDY_SECTION: MRAD

STUDY_SECTION_NAME: Maximizing Investigators' Research Award - D Study Section[MRAD]


ADMINISTERING_IC: TR

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Natural Products;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: SEATTLE

ORG_NAME: CURI BIO INC

ORG_STATE: WA

PHR: PROJECT NARRATIVE Current approaches to measuring the potency of manufactured lots of Botulinum toxin (BoT) involve laborious and ethically dubious mouse lethality assays. Organ on chip technologies based on human induced pluripotent stem cells offer an attractive solution as they can be performed rapidly and in absence of ethical concerns. In this proposal, we will develop an integrated, next-generation platform consisting of instrumentation and stem- cell based models of the neuromuscular junction that can be used for BoT potency assays.

PI_NAMEs: GEISSE, NICHOLAS ANDREW (contact)

PROGRAM_OFFICER_NAME: KREPKIY, DMITRIY

PROJECT_TERMS: Acetylcholine;Adoption;animal facility;Animals;Area;Assessment tool;Axon;Biological Assay;Biomedical Engineering;Body Regions;Botox;Botulinum Toxins;Cell Culture Techniques;cell type;Cells;Coculture Techniques;commercialization;Communication;Computer software;Cosmetics;culture plates;Data;design;Development;Devices;disease model;Dose;driving force;drug development;drug efficacy;Drug Screening;Electrodes;Engineering;Ethics;Exposure to;Frequencies;Functional disorder;high throughput screening;Human;human induced pluripotent stem cells;human model;human tissue;In Vitro;in vitro Model;in vivo;induced pluripotent stem cell;Induced pluripotent stem cell derived human neuron;Induced pluripotent stem cell derived neurons;instrumentation;Interview;manufacture;Marketing;Measurement;Measures;Medical;Methods;Modeling;Modernization;Motor Neurons;multiplex assay;Mus;Muscle;Muscle Cells;Muscle Contraction;muscle engineering;Muscle Fibers;Muscle function;National Center for Advancing Translational Sciences;Nerve;Nerve Degeneration;nerve supply;Neurodegenerative Disorders;neuromuscular;Neuromuscular Junction;neuronal cell body;Neurons;Neurotoxins;next generation;novel;novel therapeutics;organ on a chip;Output;Patients;Peripheral Nervous System Diseases;Pharmaceutical Preparations;Phase;Phenotype;Physiology;Population;pre-clinical;preclinical study;predictive modeling;prevent;Process;Production;programs;Protocols documentation;prototype;Publishing;Reproducibility;response;Safety;Sales;screening;Screening procedure;Skeletal Muscle;skills;Source;Specificity;stem cell model;Stratification;Synapses;Synaptic Cleft;System;Technology;Testing;therapy development;Time;Tissue Microarray;Toxic effect;Validation;Voice;Work;Writing

PROJECT_TITLE: High-Throughput NMJ Assay for Botox Potency Screening


NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: Seattle

ORG_NAME: TALUS BIOSCIENCE, INC.

PHR: PROJECT NARRATIVE This research aims to develop a technology to enable drug development for undruggable transcription factor proteins. Traditional tools to study these proteins have proven ineffective, so we are developing an in-cell system discovery technology that tests a drug’s ability to block disease-causing transcription factors.

PI_NAMEs: FEDERATION, ALEXANDER  (contact)

PROGRAM_OFFICER_NAME: SHARMA, KARLIE ROXANNE

PROJECT_TERMS: Address;adduct;Algorithms;Binding;Binding Proteins;Biological Assay;Biotechnology;Biotin;Businesses;cancer type;Categories;Cells;cellular engineering;Chemistry;Chromatin;Clinical Research;Clinical Trials;cofactor;comparative efficacy;Computer software;computerized tools;Coupled;Cysteine;Cystine;Data;Detection;Development;Disease;DNA;driver mutation;drug development;drug discovery;Engineering;Foundations;Functional disorder;Future;Gene Expression;Genome;Hand;Human;Human Genome;in vitro activity;Inflammation;inhibitor;innovation;Instruction;interest;KRAS2 gene;Label;Lead;lead optimization;leukemia;Libraries;Ligands;Machine Learning;Malignant Neoplasms;malignant phenotype;Mass Spectrum Analysis;Measurement;Measures;Methods;Modeling;Modernization;Mutate;Mutation;Neurologic;novel strategies;Nuclear;Nuclear Extract;Oncogenic;overexpression;Peptides;Performance;Pharmaceutical Chemistry;Pharmaceutical Preparations;Pharmacologic Substance;Phase;Preparation;programs;Protein Analysis;Proteins;Proteome;Proteomics;Publishing;Regulator Genes;Reporting;Research;Role;Sampling;Sarcoma;screening;small molecule;small molecule inhibitor;Sodium Chloride;Structural Protein;System;Talus;Technology;Testing;Tissues;tool;transcription factor;Transcription Factor Oncogene;Triage;tumor;Validation;Work

PROJECT_TITLE: Activity-based regulome profiling for the discovery of covalent transcription factor inhibitors


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

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

ORG_CITY: NEW YORK

ORG_DEPT: PEDIATRICS

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: PROJECT NARRATIVE Mannosemetabolism as a regulator of hepatic stellate cell activation and fibrosis Chronic liver disease can lead to irreversible scarring of the liver, which can lead to liver failure, liver cancer, and necessitate liver transplantation. Currently, there are no approved medical treatments to effectively reverse scarring. This project proposes to investigate a new pathway involved in liver scar formation that can potentially lead to new drug targets.

PI_NAMEs: CHU, JAIME C (contact)

PROGRAM_OFFICER_NAME: BURGESS-BEUSSE, BONNIE L

PROJECT_TERMS: Address;antifibrotic treatment;Apoptosis;Attenuated;attenuation;Automobile Driving;Biology;cancer cell;Catabolism;Cell Death;Cell Proliferation;cell type;Cells;Cellular biology;Child;Childhood;chronic liver disease;Cicatrix;Cirrhosis;Clinical;cohort;Congenital Disorders;Data;Diabetes Mellitus;Disease;Dose;drug discovery;efficacy evaluation;Enzymes;Ethanol;Exposure to;fibrogenesis;Fibrosis;Genetic;glycosylation;Goals;Hepatic Stellate Cell;Hepatitis B Virus;Hepatocyte;Hepatology;Human;In Vitro;in vivo;inorganic phosphate;Isomerase;Link;Liver;Liver diseases;Liver Failure;Liver Fibrosis;liver metabolism;liver transplantation;Malignant neoplasm of liver;Malignant Neoplasms;Mannose;Mediating;Mediator;Medical;Metabolic;Metabolic Pathway;Metabolism;Minor;Modeling;mutant;Mutation;new therapeutic target;non-alcoholic fatty liver disease;novel;Obesity;Pathway interactions;Phenotype;prevent;Public Health;Rattus;Regulation;response;restoration;Rodent;Rodent Model;Role;sugar;Supplementation;Testing;Therapeutic;Thioacetamide;Vitamin A;Zebrafish

PROJECT_TITLE: Mannose metabolism as a regulator of hepatic stellate cell activation and fibrosis

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


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

ORG_DEPT: SURGERY

PHR: Project narrative While it is known that fatty livers are particularly vulnerable to injury, incomplete understanding of the molecular and cellular mechanisms underlying injury limits development of strategies for effective prevention and treatment of injury in fatty livers. This proposal will investigate the function of ATP citrate lyase, an important enzyme critical for cellular energy metabolism, in liver cells using cell biological and transgenic techniques. The information generated from this project will provide new insights relevant to prevention and treatment strategies for liver injury in patients with non-alcoholic fatty liver disease.

PI_NAMEs: ZHANG, WEIZHEN  (contact)

PROGRAM_OFFICER_NAME: SHERKER, AVERELL H

PROJECT_TERMS: 5'-AMP-activated protein kinase;Accountability;Acetyl Coenzyme A;Apoptosis;Area;ATP Citrate (pro-S)-Lyase;Biological;Cell Nucleus;Cells;Cleavage Under Targets and Release Using Nuclease;Couples;Data;design;Development;Discipline;Disease;endoplasmic reticulum stress;Energy Metabolism;Enzymes;Epigenetic Process;Fatty Liver;G-Protein-Coupled Receptors;Genes;genetic approach;Genetic Transcription;Hepatic;Hepatocyte;hepatocyte injury;Histone Acetylation;Impairment;Injury;insight;Ischemia;Leucine-Rich Repeat;Ligands;Lipids;Liver;liver injury;Mediating;Medical;Molecular;Morbidity - disease rate;mortality;non-alcoholic fatty liver disease;novel;Nuclear;Nuclear Translocation;Pathway interactions;Patients;pharmacologic;Phosphorylation;Phosphorylation Site;Physiological;Physiology;Prevention;Prevention strategy;Proteins;Reperfusion Injury;Resistance;response;restoration;Signal Transduction;Stress;System;Techniques;transcriptome sequencing;Transgenic Mice;Transgenic Organisms;treatment strategy

PROJECT_TITLE: Nuclear ATP citrate lyase and ischemia/reperfusion injury in steatotic liver


NIH_SPENDING_CATS: Aging;Cardiovascular;Heart Disease

ORG_CITY: CHARLESTON

ORG_NAME: FIBROTHERAPEUTICS, INC.

ORG_STATE: SC

PHR: Narrative Fibrosis (the stiffening of tissues due to collagen overproduction/deposition) and blood vessel leakage are major contributors to the deficits in ventricular function that occur in Heart Failure (HF). We have been working on novel, modified versions suitable for drug development of a biologic peptide (called CSD) that we have already shown to suppress fibrosis and blood vessel leakage and to improve ventricular function in multiple model systems for HF. In this proposal, based on its beneficial effects in two model systems, we will select a Lead Compound for further development as a treatment for HF from among four candidates that we have designed and, additionally, we will evaluate the potential toxicity of this Lead Compound in a Maximum Tolerated Dose experiment.

PI_NAMEs: HOFFMAN, STANLEY R (contact)

PROGRAM_OFFICER_NAME: SHI, YANG

PROJECT_TERMS: absorption;Active Sites;Address;Adult;Affect;Age;Aging;aging related;Amino Acids;Angiotensin II;aorta constriction;Biological;Biological Models;Blood Vessels;Body Weight;Catheters;caveolin 1;Cells;Characteristics;Collagen;coronary fibrosis;Dependence;Deposition;design;Detection;Development;Diagnosis;Disease;Dose;drug development;Echocardiography;efficacy evaluation;EFRAC;Enzymes;Excretory function;experimental study;Extravasation;Fibrosis;Future;Heart;Heart Diseases;Heart failure;Heart Hypertrophy;High Pressure Liquid Chromatography;Immunoglobulin G;improved;In Vitro;in vivo;Infusion procedures;Isoproterenol;Lead;Length;lifetime risk;Lung Diseases;Maximum Tolerated Dose;Medical Care Costs;Metabolism;Methods;Modeling;Modification;mortality;mouse model;Mus;novel;novel lead compound;novel therapeutics;Occupations;old mice;Pathologic;Patients;Peptides;pharmacologic;Pharmacology;phase 2 study;Phosphotransferases;Population;pressure;Prevalence;Production;Property;prophylactic;Protein Tyrosine Kinase;Proteolysis;Pulmonary Fibrosis;Regulation;Relaxation;Safety;scaffold;Shortening Fraction;Side;Specificity;success;Tertiary Protein Structure;Testing;Therapeutic;Therapeutic Index;therapeutic target;Time;Tissues;Toxic effect;Toxicology;uptake;Ventricular Function;Water;Weight

PROJECT_TITLE: Novel Therapeutics for Heart Failure: Modified, Water-Soluble Caveolin-1 Scaffolding Domain Peptides with Improved Characteristics for Drug Development


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Chronic Liver Disease and Cirrhosis;Diabetes;Digestive Diseases;Genetics;Hepatitis;Liver Disease;Nutrition;Obesity;Substance Misuse

ORG_CITY: Los Angeles

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

ORG_STATE: CA

PHR: Fatty liver disease occurs in about 25% in the general population of the United States and as high as 70% in the obese population and those with Diabetes; and in individual who consume alcohol. With the increase in obesity rate and continued excessive drinking behavior in the US population, fatty liver is in line to become the leading cause of liver transplantation in the next 10 years. This project will study the molecular changes occurring with fatty liver using mouse models. We also designed an inhibitor to block the signal that we have discovered. We expect this inhibitor to exhibit therapeutic effect at treating fatty liver disease.

PI_NAMEs: STILES, BANGYAN  (contact)

PROJECT_TERMS: Address;Alcohol consumption;Alcoholic Liver Diseases;Alcoholic steatohepatitis;Alcohols;Anabolism;Binding;Bioenergetics;Biogenesis;Biology;Cell Physiology;ChIP-seq;Chromatin;Chronic;Cirrhosis;Citric Acid Cycle;Complex;CREB1 gene;design;Development;Diabetes Mellitus;Diet;diet-induced obesity;Disease;drinking behavior;Dyslipidemias;Enzymes;estrogen-related receptor;Estrogens;Ethanol;Exhibits;Fatty Acids;Fatty Liver;fatty liver disease;feeding;Fibrosis;Functional disorder;functional outcomes;gain of function;Gene Expression Regulation;General Population;Genes;Genetic Models;Genetic Transcription;glucose metabolism;Goals;Heavy Drinking;High Fat Diet;In Vitro;in vivo;Individual;Inflammation;inhibitor;Insulin;Insulin Resistance;insulin signaling;Insulin-Like Growth Factor I;lipid biosynthesis;lipid metabolism;lipidomics;Lipids;Liver;Liver diseases;liver injury;liver transplantation;loss of function;Malignant neoplasm of liver;Mediating;member;Metabolic;Metabolic Diseases;Metabolic dysfunction;Metabolic syndrome;Metabolism;Mitochondria;Modeling;Modification;Molecular;mouse model;Mus;Mutation;non-alcoholic fatty liver disease;Non-Insulin-Dependent Diabetes Mellitus;nonalcoholic steatohepatitis;novel;Nuclear Orphan Receptor;Nuclear Receptors;Nylons;obese person;Obesity;oxidation;Oxidative Phosphorylation;oxidized lipid;particle;Pathology;patient subsets;Patients;Phosphorylation;Physiological;PI3K/AKT;Play;Population;Precipitation;Production;promoter;Property;Protein Isoforms;Proto-Oncogene Proteins c-akt;Reactive Oxygen Species;Receptor Inhibition;Regulation;Reporting;Resistance;Role;Signal Pathway;Signal Transduction;small molecule;small molecule inhibitor;Steatohepatitis;System;Testing;Therapeutic Effect;therapeutic evaluation;transcription factor;Transcriptional Regulation;transcriptome sequencing;translational approach;Triglycerides;United States;Up-Regulation

PROJECT_TITLE: The Role of ERRa in liver lipid dysfunction and pathology


NIH_SPENDING_CATS: Digestive Diseases;Digestive Diseases - (Gallbladder);Liver Disease;Rare Diseases

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Project Narrative The main aim of this proposal is to develop new potential therapeutic approaches for polycystic liver disease and cholangiocarcinoma. Our proposed studies will uncover novel and generalizable information on the fundamental mechanisms of ciliary dependent regulation of EGFR signaling.

PI_NAMEs: GRADILONE, SERGIO A (contact)

PROJECT_TERMS: Acetylation;alpha Tubulin;Autophagocytosis;bile duct;biliary tract;Biliary Tract Diseases;Biogenesis;CBL gene;cell growth;Cell Line;cell motility;Cells;Cholangiocarcinoma;cholangiocyte;Cilia;Clinical Trials;combinatorial;Communication;Cytoplasm;Data;Deacetylase;Deacetylation;Defect;design;Development;Disease;Ductal Epithelial Cell;EGF gene;Environment;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;Epithelial Cells;Erlotinib;experimental study;Family member;Foundations;Functional disorder;Goals;HDAC6 gene;Histone Deacetylase;In Vitro;in vivo;inhibition of autophagy;Inhibition of Cell Proliferation;inhibitor;Leucine Zippers;Liver;Lysine;malformation;migration;Molecular;multisensory;Mus;Needs Assessment;Normal Cell;novel;novel therapeutic intervention;novel therapeutics;Organelles;overexpression;Pathogenesis;Pathologic;patient derived xenograft model;polycystic liver disease;pre-clinical;Process;Proteins;receptor;Receptor Inhibition;Receptor Signaling;Regulation;restoration;Rodent Model;Role;Sensory;Signal Pathway;Signal Transduction;SIRT1 gene;Structure;Testing;Therapeutic;transcription factor;ubiquitin-protein ligase;Ubiquitination;Work

PROJECT_TITLE: Primary cilia loss in bile duct cells- the interplay with the autophagy machinery

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-R(04)]


NIH_SPENDING_CATS: Biotechnology;Digestive Diseases;Genetics;HIV/AIDS;Hematology;Infectious Diseases;Liver Disease

ORG_CITY: CORAL GABLES

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: Project Narrative This project will assess whether cells within the liver serve as viral reservoirs in HIV- infected individuals. The project will use novel molecular approaches to assess HIV sequences within these anatomic sites and whether they are replication competent. This information will provide a fuller understanding of how HIV is able to persist under antiretroviral therapy.

PI_NAMEs: STEVENSON, MARIO  (contact);THOMAS, EMMANUEL

PROGRAM_OFFICER_NAME: DOO, EDWARD

PROJECT_TERMS: Address;Adopted;Alleles;Anatomy;Antibodies;antiretroviral therapy;Area;Binding;Blood specimen;CD4 Positive T Lymphocytes;Cell Compartmentation;Cell membrane;Cells;Cellular Tropism;Characteristics;Clinical;design;Discrimination;Disease remission;Exhibits;Genetic Polymorphism;Genome;HIV;HIV-1;HIV/AIDS;Immune system;In Vitro;Individual;Infection;insight;Interruption;Kupffer Cells;Length;Libraries;Ligands;Liver;Location;Macrophage;Membrane;Methods;Molecular;molecular clock;Molecular Cloning;Myelogenous;Myeloid Cells;Nature;novel;novel strategies;personalized approach;Phenotype;Phylogenetic Analysis;Plasma;Plasma Cells;Polymerase;Proviruses;Recombinants;Research;Resources;Role;Sampling;Structure;Tissues;Transplantation;Variant;Viral;viral rebound;Viral reservoir;Viremia;Virion;Virus

PROJECT_TITLE: Defining a Role for Liver Myeloid Cells in Viral Persistence under ART


NIH_SPENDING_CATS: Cancer;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Hepatitis;Hepatitis - C;Infectious Diseases;Liver Cancer;Liver Disease;Prevention;Rare Diseases

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: Project Narrative Cellular crosstalk is a process through a message transmitted between cells. Intercellular crosstalk of hepatocytes and non-parenchymal cells (i.e. Mφ and LSEC) is crucial for the maintenance of liver homeostasis. Under the pathological condition, hepatocyte damage results in the activation of fibrotic Mφ and LSEC. Thereby these cells play a critical role in the control of hepatic inflammation and the development of liver fibrosis. Exosomes are small membrane-bound extracellular vesicles and serve as natural carriers of signaling molecules such as cytokines for prompting cellular crosstalk. This project will identify a major cellular and molecular mechanism for the role of exosomes released from HCV-infected hepatocytes in promoting intercellular communication with non-parenchymal cells (i.e. Mφ and LSEC), leading to the development of liver fibrosis. The findings from our proposed research will provide a rationale basis of novel immunotherapeutic strategies that target molecules inducing pro-fibrotic factors through HCV-derived exosomes.

PI_NAMEs: HAHN, YOUNG S. (contact)

PROJECT_TERMS: Affect;Anti-Inflammatory Agents;Anti-viral Agents;Apoptotic;Automobile Driving;Binding;Biological Markers;Bypass;CASP3 gene;Cell Differentiation process;Cells;Chronic;Chronic Hepatitis C;chronic liver disease;Cirrhosis;Clinical;Coculture Techniques;cytokine;Data;design;Development;Disease Progression;end stage liver disease;Endothelial Cells;Equilibrium;exosome;extracellular vesicles;Fibrosis;Frequencies;Generations;Goals;Health;Hepatic;Hepatic Stellate Cell;Hepatitis C;Hepatitis C Therapy;Hepatitis C virus;Hepatocyte;Homeostasis;Human;humanized mouse;Immune;immunoregulation;Immunotherapeutic agent;In Vitro;in vivo;Inflammatory;Inflammatory Response;insight;intercellular communication;Life;Liver;liver development;Liver diseases;Liver Fibrosis;liver inflammation;Macrophage;Maintenance;Mediating;Membrane;MicroRNAs;Molecular;monocyte;mouse model;nanoparticle delivery;new therapeutic target;novel;novel therapeutic intervention;Outcome;Pathogenesis;Pathogenicity;Pathologic;Pathway interactions;Patients;peripheral blood;Persons;Plasminogen Inactivators;Play;Population;Pre-Clinical Model;prevent;Prevention;Primary carcinoma of the liver cells;Principal Investigator;Process;Production;Profibrotic signal;programs;Regulation;Reporting;Research;Risk;Role;Severities;Signal Transduction;Signaling Molecule;stellate cell;Surface;Testing;Therapeutic;Therapeutic Agents;Transforming Growth Factor beta;transmission process;Virus;Work

PROJECT_TITLE: Role of HCV exosomes in intercellular communication

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


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;Hepatitis;Liver Cancer;Liver Disease;Nanotechnology;Nutrition;Rare Diseases

ORG_CITY: RICHMOND

ORG_DEPT: GENETICS

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

PHR: Narrative The proposal aims at analyzing the role of macrophage AEG-1 in nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC), interrogate cysteine palmitoylation as a regulatory mechanism for AEG-1 function, and evaluate inhibition of AEG-1 in hepatocytes and macrophages as a therapeutic strategy for NASH and NASH-HCC. These studies will provide novel mechanistic insights into AEG-1 function and facilitate development of a novel therapeutic strategy for NASH.

PI_NAMEs: SARKAR, DEVANAND  (contact)

PROGRAM_OFFICER_NAME: GARCIA, MARTHA

PROJECT_TERMS: Address;Adipocytes;Adipose tissue;Astrocytes;Biochemical;Biological Assay;Biology;Cells;chronic liver disease;Cirrhosis;Clinic;Clinical Trials;Cysteine;cytokine;Development;Diet;Diethylnitrosamine;Disease;Enzymes;Event;experimental study;Failure;Fatty acid glycerol esters;Fatty Acids;Gene Expression;Genes;global health;Hepatocyte;High Fat Diet;Human;Impairment;Inflammation;Inflammatory;insight;Interleukin-1 beta;Intervention;knock-down;Knock-in Mouse;Knockout Mice;lipid biosynthesis;Lipolysis;Liver;loss of function;Macrophage;Macrophage Activation;Molecular;Monitor;mouse model;Mus;Mutate;Myeloid Cells;nanoparticle;nanoparticle delivery;nonalcoholic steatohepatitis;Nonesterified Fatty Acids;novel;novel therapeutic intervention;Oncogenes;oxidation;palmitoylation;Pathogenesis;Play;Post-Translational Protein Processing;PPAR alpha;Preventive;Primary carcinoma of the liver cells;Process;Proteins;Publishing;Resistance;RNA Interference;Role;Seminal;Serine;single-cell RNA sequencing;Small Interfering RNA;sugar;targeted treatment;Testing;Therapeutic;Therapeutic Intervention;therapeutically effective;TNF gene;Transgenic Mice;Translations;Treatment Efficacy;Triglycerides;tumorigenic;Western World

PROJECT_TITLE: The role of AEG-1 in NASH and NASH-HCC


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Congenital Structural Anomalies;Digestive Diseases;Pediatric

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: COLUMBIA UNIV NEW YORK MORNINGSIDE

PHR: PROJECT NARRATIVE The emergence of precise physical patterns during embryonic development is critical for the birth of a healthy and fully functional organism. The present application addresses this inherently multidisciplinary problem in the context of looping of the small intestine, a process driven by mechanical buckling of the initially straight tube that allows the lengthy intestine to be packaged within the abdomen. Advancing our understanding of how molecular cues control forces to shape the embryo, and the potential biological importance of the forces themselves, may shed light on the underlying causes of congenital disorders such as midgut volvulus, and provide inroads to the manipulation of forces to engineer tissues and organs in the lab.

PI_NAMEs: NERURKAR, NANDAN L (contact)

PROGRAM_OFFICER_NAME: GREENWEL, PATRICIA

PROJECT_TERMS: 3-Dimensional;Abdomen;Actomyosin;Address;Adolescence;Area;Automobile Driving;Back;Behavior;Biological;Biology;Bioreactors;Birth;body cavity;cell behavior;Cell Count;Cell Proliferation;Cell Size;cell type;Cell Volumes;Cells;Cerebral cortex;Chick;Collecting Tube;Congenital Abnormality;Congenital Disorders;Cues;Dependence;design;Development;driving force;Elasticity;Embryo;Embryonic Development;Engineering;experimental study;Extracellular Matrix;Feedback;follow-up;FRAP1 gene;Genes;Geometry;Goals;Growth;Hand;insight;Intestinal Obstruction;Intestinal Volvulus;Intestines;Length;Link;mathematical model;Measurement;Measures;mechanical drive;mechanical force;Mechanics;Mediating;Mesentery;Microbial Biofilms;Midgut;Molecular;Morphogenesis;Morphology;mortality risk;multidisciplinary;Operative Surgical Procedures;Organ;Organism;Organogenesis;Pathway interactions;Pattern;Pharmacological Treatment;Phenotype;physical process;physical property;Physics;Play;Prevalence;Process;Proliferating;Regenerative Medicine;Regulation;repaired;Role;Shapes;Signal Pathway;Signal Transduction;Small Intestines;Specific qualifier value;Stereotyping;stereotypy;Stress;Stretching;Study models;Surface;Testing;Tissue Engineering;Tissues;Tube;Work

PROJECT_TITLE: Molecular control of mechanical forces driving buckling morphogenesis of the small intestine

STUDY_SECTION_NAME: Development - 1 Study Section[DEV1]


NIH_SPENDING_CATS: Autoimmune Disease;Digestive Diseases;Inflammatory Bowel Disease

ORG_CITY: CLEVELAND

ORG_DEPT: PATHOLOGY

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: Public Health Relevance  Inflammatory bowel disease (IBD) affects more than a million people in the United States, alone, and there is presently no cure, with limited preventive measures for this condition. We recently discovered that the inflamed mouse and human colonic epithelium produces extracellular vesicles containing IL-1 family cytokines, including IL-1 and IL-18, that exacerbate T cell-mediated colitis and cause anti-TNF therapy failure. This application aims to provide mechanistic insight into this pathogenic cross-talk between intestinal epithelial cells and T cells, and to identify potential targets to address anti-TNF therapy failure using murine colitis models and clinical specimens from IBD patients.

PI_NAMEs: PIZARRO, THERESA TORRES (contact)

PROGRAM_OFFICER_NAME: PERRIN, PETER J

PROJECT_TERMS: adaptive immune response;Address;Affect;Anti-Tumor Necrosis Factor Therapy;Area;autocrine;Binding Proteins;Biogenesis;Biological Response Modifiers;Biopsy;Caspase;CDC37 gene;Cells;Cellular Stress;Chronic;Clinical;Colitis;Colon;Colonic inflammation;Communications Media;Complex;cytokine;Data;Detection;dextran sulfate sodium induced colitis;Disease;Environment;Environmental Risk Factor;Epithelial Cells;Epithelium;Etiology;exosome;extracellular vesicles;Family;Family member;gastrointestinal epithelium;Granulocyte-Macrophage Colony-Stimulating Factor;gut inflammation;Human;IL18 gene;Immune;Immune response;Inflammasome;Inflammation;Inflammatory;Inflammatory Bowel Diseases;Inflammatory Response;injured;insight;Interferon Type II;Interferons;Interleukin-1;Intestinal Content;intestinal epithelium;Knockout Mice;Length;Lipid Binding;Lytic;Macrophage;Mediating;member;Modeling;Molecular;Molecular Chaperones;Mucous Membrane;murine colitis;Mus;N-terminal;Nonlytic;novel;Organoids;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Persons;Play;Polyubiquitination;pre-clinical research;Preventive measure;Production;Proteomics;public health relevance;recruit;Resistance;response;Role;Signal Transduction;Source;Specimen;Stimulus;success;Surface;T-Cell Activation;T-Lymphocyte;Testing;Therapeutic;Tissues;TNF gene;Treatment Failure;ubiquitin-protein ligase;United States;Vesicle

PROJECT_TITLE: The pathogenic roles of GSDMD-dependent gut epithelium extracellular vesicles in IBD

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-P(02)]


NIH_SPENDING_CATS: Autoimmune Disease;Clinical Research;Crohn's Disease;Digestive Diseases;Estrogen;Genetics;Immunotherapy;Inflammatory Bowel Disease

PHR: Project Narrative Steroid sex hormones such as 17β-estradiol (estrogen) are important regulators of immune responses. Although estrogen is generally immunoprotective, our data show that it contributes to the pathogenesis of chronic inflammatory diseases such as IBD by impairing the differentiation and function of regulatory T cells (Tregs). This project seeks to identify the mechanism(s) by which altered estrogen signaling impairs Treg- mediated immunosuppression in the chronically inflamed intestine, with the ultimate goal of developing novel approaches for the treatment of IBD.

PI_NAMEs: GOODMAN, WENDY ANN (contact)

PROJECT_TERMS: Address;Adoptive Transfer;Antigens;Area;Backcrossings;Biological Assay;Biological Response Modifiers;Biopsy;Candidate Disease Gene;CD4 Positive T Lymphocytes;Cell Physiology;Cell Separation;Cells;chromatin immunoprecipitation;Chronic;chronic inflammatory disease;Co-Immunoprecipitations;Colitis;Complex;Crohn's disease;Data;Defect;Disease;Environment;Environmental Risk Factor;Equilibrium;ESR1 gene;Estradiol;Estrogen Receptor 2;Estrogens;Event;Exhibits;experimental study;Female;FOXP3 gene;Frequencies;Gene Expression Regulation;Genetic;Genetic Transcription;Goals;Gonadal Steroid Hormones;gut inflammation;Homeostasis;Human;Ileitis;Immune;Immune response;Immune Tolerance;immunoregulation;Immunosuppression;Impairment;improved;in vivo;Inflammation;Inflammatory;Inflammatory Bowel Diseases;insight;Intestinal Mucosa;Intestines;Knockout Mice;Knowledge;loss of function;Mediating;Membrane;microbial;Modeling;Molecular;murine colitis;Mus;novel;novel strategies;Nuclear Receptors;Pathogenesis;Pathway interactions;Patients;Peripheral;Phenotype;Predisposition;prevent;Publishing;receptor;Regulatory T-Lymphocyte;Resistance;response;Role;SAMP mouse;Sampling;Sequence Homology;sex;Signal Transduction;T cell differentiation;T cell response;T-Lymphocyte;Technology;Testing;Tissues;transcriptional reprogramming;transcriptome sequencing;Transfection;Transforming Growth Factor beta;Ulcerative Colitis;Western Blotting;Work

PROJECT_TITLE: Estrogen-mediated immune regulation in human and experimental inflammatory bowel disease

STUDY_SECTION: GMPB

STUDY_SECTION_NAME: Gastrointestinal Mucosal Pathobiology Study Section[GMPB]


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);Bioengineering;Biomedical Imaging;Brain Disorders;Dementia;Genetics;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Women's Health Research

ORG_CITY: Chicago

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: Project Narrative This multidisciplinary MPI program will use in silico computational and in vivo experimental approaches to study the molecular, cellular and circuit mechanisms of sex-, ApoE- and amyloidosis- dependent hyperexcitability in humans and animal models of Alzheimer’s disease and the therapeutic efficacy of the antiseizure drug Levetiracetam.

PI_NAMEs: LAZAROV, ORLY ;LEOW, ALEX  (contact);ZHAN, LIANG

PROGRAM_OFFICER_NAME: DIBATTISTA, AMANDA

PROJECT_TERMS: Address;Affect;Age;aging related;Alleles;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease patient;Amyloidosis;Animal Model;Anisotropy;Anticonvulsants;Apolipoprotein E;apolipoprotein E-4;Astrocytes;Back;Behavior;biophysical model;biophysical properties;Biophysics;Brain;Brain imaging;Calcium;Cerebrum;Cognition;Cognitive;Cognitive deficits;cognitive function;computer framework;connectome;connectome data;Data;Deterioration;Diffusion Magnetic Resonance Imaging;disease phenotype;drug efficacy;epileptiform;Equilibrium;excitatory neuron;Exhibits;Experimental Models;Female;Functional Magnetic Resonance Imaging;Genetic Transcription;Goals;Hippocampus;Human;human model;Image;Immunohistochemistry;improved;in silico;in situ sequencing;in vivo;indexing;inhibitory neuron;insight;Interneurons;Intervention;Knock-in;Knock-in Mouse;Levetiracetam;Link;Magnetic Resonance Imaging;male;Mediating;Memory impairment;Microglia;middle age;Midlife women;Modeling;Molecular;mouse model;multidisciplinary;multimodality;Mus;Myelin;myelination;neural;Neurons;neuropathology;Neurosciences;neurotoxicity;novel;Oligodendroglia;Output;Pathology;Phase;Phenotype;Predisposition;prevent;Process;programs;Publishing;Reporting;response;Rest;Selection for Treatments;sex;Sex Differences;simulation;Stains;Stimulus;synaptic function;tau Proteins;Testing;Therapeutic;Time;transcriptomics;Transgenic Mice;Translating;Treatment Efficacy;Treatment Protocols;Western Blotting;Woman

PROJECT_TITLE: Connecting Neuronal Hyperexcitability and Sex Differences in Alzheimer's Disease (AD) using biophysically-informed in-silico brain simulations and experimental data from mouse models of AD

STUDY_SECTION_NAME: Special Emphasis Panel[ZAG1 ZIJ-2 (M2)]


NIH_SPENDING_CATS: Microbiome;Nutrition;Obesity

ORG_CITY: PROVIDENCE

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: The proposed research is highly relevant to public health because defining how antibiotic-mediated microbiome disruption contributes to complications such as obesity and diabetes may, in the long run, identify ways to alleviate these conditions for millions of Americans. This work will define the impacts of antibiotics on the metabolic environment of the murine gut, host metabolite availability and weight gain. In addition to generating fundamental scientific discoveries, this research will also fulfill NIH goals by generating a mechanistic perspective on how antibiotics contribute to diabetes, digestive diseases, nutritional disorders, and obesity.

PI_NAMEs: BELENKY, PETER  (contact)

PROGRAM_OFFICER_NAME: LUNSFORD, DWAYNE

PROJECT_TERMS: Adult;American;Amoxicillin;Animals;Antibiotic Therapy;Antibiotics;antimicrobial;Bacteria;Bacteroidetes;beta-Lactams;Blood Glucose;Butyrates;Cellular Metabolic Process;Child;Clinical;clinically relevant;combat;Communities;cost;Data;Diabetes Mellitus;Diet;dietary;Dietary Component;Digestive System Disorders;Dose;Environment;Farm;Fermentation;fighting;Firmicutes;Genetic Transcription;Glucose;Goals;gut bacteria;gut microbiome;Health;health determinants;Human;Hyperglycemia;Inflammation;Inflammatory Response;insight;Insulin Resistance;Intervention;Laboratory mice;Lead;Link;Livestock;Malnutrition;Mediating;Metabolic;Metabolic dysfunction;Metabolism;metabolome;Methodology;microbial community;microbial composition;microbiome;microbiome alteration;microbiome composition;microbiota;Morbidity - disease rate;Motivation;multiple omics;Mus;Nutrient;nutrient absorption;Nutrition Disorders;Obesity;Outcome;pathobiont;pathogen;Penicillins;Pharmaceutical Preparations;Physiology;Probiotics;Public Health;Publishing;Research;response;restoration;Signaling Molecule;systemic inflammatory response;Taxonomy;Testing;theories;Toxic effect;United States National Institutes of Health;Vitamins;Weight;Weight Gain;Work;Xenobiotics

PROJECT_TITLE: Relating impacts of antibiotics on the gut metabolome and microbiome to host physiology and weight

STUDY_SECTION: INMP

STUDY_SECTION_NAME: Integrative Nutrition and Metabolic Processes Study Section[INMP]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Biotechnology;Brain Disorders;Cannabinoid Research;Depression;Drug Abuse (NIDA only);Genetics;Human Genome;Major Depressive Disorder;Mental Health;Mental Illness;Neurosciences;Serious Mental Illness;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Substance Misuse

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative In the United States, millions of people use cannabis and there is now convincing evidence linking its use with depression and suicidal behavior. By combining human postmortem genomics, MPRA genetic engineering, and human induced pluripotent stem cell derived brain organoids, we propose to test the molecular and functional impact of cannabis use perturbing the genotype of MDD risk alleles. We hope to find insights into the mechanism of disease initiation and progression of MDD in people with substance use disorders.

PI_NAMEs: GIRGENTI, MATTHEW J (contact)

PROGRAM_OFFICER_NAME: POLLOCK, JONATHAN D

PROJECT_TERMS: Automobile Driving;Autopsy;Biological Assay;Brain;Brain Diseases;Brain region;Cannabis;cell type;Chromatin;comorbidity;Development;Disease;DNA Sequence Alteration;Drug usage;epigenomics;Gene Expression Regulation;Genes;genetic approach;Genetic Engineering;genome wide association study;Genomic Segment;Genomics;Genotype;Human;human induced pluripotent stem cells;innovation;insight;Lead;Link;Major Depressive Disorder;marijuana legalization;marijuana use;marijuana use disorder;Mental Depression;Mental disorders;Modeling;Molecular;new therapeutic target;Organoids;Pathogenesis;Persons;Predisposition;Prefrontal Cortex;Recording of previous events;Reporting;reverse genetics;Risk;risk variant;Role;Signal Transduction;Stress;stressor;Substance Use Disorder;suicidal behavior;Suicide;Testing;THC exposure;transcriptomics;United States;Ventral Striatum

PROJECT_TITLE: Functional convergence following disruption of diverse genes associated with cannabis use and major depression

STUDY_SECTION_NAME: Special Emphasis Panel[ZDA1 IXR-N (M1)]


ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative Obesity is a major public health concern as it increases the risk for a number of common diseases such as type 2 diabetes, heart disease, stroke and certain forms of cancer. Obesity results from the interaction of the environment with a genetic predisposition and large-scale efforts have recently pointed at regions in the human genome in which genetic variations predispose humans to obesity. Our studies are aimed at determining how these genetic variations are involved in obesity and how this knowledge could be harvested for new obesity treatments.

PI_NAMEs: AHITUV, NADAV ;VAISSE, CHRISTIAN  (contact)

PROGRAM_OFFICER_NAME: PAWLIKOWSKA, LUDMILA SYLWIA

PROJECT_TERMS: Address;Affect;Anatomy;ATAC-seq;Biological Assay;Body Weight;cancer type;candidate identification;Cause of Death;Central Nervous System;ChIP-seq;Chromosome Mapping;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;CRISPR-mediated transcriptional activation;differential expression;Disease;Eating;Elements;Environment;Family Study;Food Intake Regulation;Gene Expression;Genes;Genetic Predisposition to Disease;genetic variant;Genetic Variation;Genome;genome wide association study;Genomics;Harvest;Heart Diseases;Heritability;High Fat Diet;Homeostasis;Human;Human Genome;Hypertension;Hypothalamic structure;in vivo;indexing;Injections;Knowledge;Laboratories;Link;Malignant Neoplasms;Maps;Metabolic;Modeling;Mus;Myocardial Infarction;Neurons;Non-Insulin-Dependent Diabetes Mellitus;Nucleic Acid Regulatory Sequences;Obesity;obesity treatment;Phenotype;Population;Protocols documentation;Public Health;Recombinant adeno-associated virus (rAAV);Regulation;Regulatory Element;Resources;Risk;Role;Single Nucleotide Polymorphism;Stroke;Technology;Testing;Therapeutic;therapeutic evaluation;therapeutic target;transcriptome;transcriptome sequencing;Twin Studies;Untranslated RNA;Variant;Weight;Weight Gain;Work

PROJECT_TITLE: From Obesity GWAS to therapeutic targets

STUDY_SECTION: GHD

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


NIH_SPENDING_CATS: Autoimmune Disease;Digestive Diseases;Infectious Diseases;Inflammatory Bowel Disease;Microbiome

ORG_CITY: RIVERSIDE

ORG_NAME: UNIVERSITY OF CALIFORNIA RIVERSIDE

PHR: Project Narrative: Alterations in intestinal microbes are critical factors contributing to many chronic inflammatory conditions such as Inflammatory Bowel Disease (IBD), celiac disease, Type 1 diabetes, and rheumatoid arthritis, which collectively affect 2.01% of the U.S. population. We have discovered a completely novel role for the protein tyrosine phosphatase non-receptor type 2 (PTPN2) gene, a candidate gene for all of these autoinflammatory conditions, in restricting expansion of an IBD-associated pathobiont, adherent-invasive E. coli (AIEC). In this proposal, we will use novel in vivo and in vitro model systems to mechanistically define the cellular and molecular mechanisms by which loss of PTPN2 activity increases host epithelial cell susceptibility to AIEC invasion, and identify if clinically approved JAK inhibitors can be repurposed to alleviate this risk event.

PI_NAMEs: MCCOLE, DECLAN  (contact)

PROGRAM_OFFICER_NAME: SHEA-DONOHUE, TEREZ

PROJECT_TERMS: Adherent Invasive Escherichia coli;Affect;American;Anti-Bacterial Agents;anti-microbial peptide;antimicrobial;Architecture;autoinflammatory;autoinflammatory diseases;Autophagocytosis;biological adaptation to stress;Biological Models;Candidate Disease Gene;Celiac Disease;Cell Physiology;cell type;Cells;Chronic;Clinical;cohort;Colitis;Data;Defect;Defense Mechanisms;Development;Disease;dysbiosis;endoplasmic reticulum stress;Enterocytes;Epithelial Cells;Epithelium;Escherichia coli Infections;Event;Generations;Genes;Genetic;Goals;Goblet Cells;gut microbes;gut microbiota;Homeostasis;host-microbe interactions;Human;human model;IL18 gene;Immune;in vitro Model;in vivo;Infection;Inflammatory;Inflammatory Bowel Diseases;inhibitor;Insulin-Dependent Diabetes Mellitus;Integration Host Factors;Interferons;interleukin-22;intestinal barrier;intestinal epithelium;Intestinal Mucosa;Intestines;Invaded;Knockout Mice;Large Intestine;loss of function;Microbe;microbial;microbial homeostasis;microbiome composition;Molecular;mouse model;Mucous body substance;Mus;novel;novel strategies;Outcome;Paneth Cells;pathobiont;pathogen;Patients;Penetration;Permeability;Population;Predisposition;preservation;Production;Property;Protein Tyrosine Phosphatase;Recovery;Regulation;Reporting;response;Rheumatoid Arthritis;Risk;Role;Signal Transduction;Single Nucleotide Polymorphism;single-cell RNA sequencing;Small Intestines;stem cell biomarkers;Stimulus;Testing;Variant

PROJECT_TITLE: A Novel Role for PTPN2 in Intestinal Epithelial Barrier Regulation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-KUDS-P(03)]


ORG_CITY: LOS ANGELES

ORG_NAME: CEDARS-SINAI MEDICAL CENTER

PHR: Project Narrative Respiratory diseases are the third leading cause of death and a major contributor to morbidity. Therefore, maintaining a strong biomedical workforce in pulmonary research is necessary to elucidate mechanisms of disease and discover novel therapies. The Multidisciplinary Pulmonary Research Training Program provides a structured environment for early career investigators to train with mentors established in diverse areas of respiratory disease research.

PI_NAMEs: CHEN, PETER  (contact);PARKS, WILLIAM C

PROGRAM_OFFICER_NAME: KALANTARI, ROYA


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Eye Disease and Disorders of Vision;Physical Injury - Accidents and Adverse Effects

ORG_DEPT: OPHTHALMOLOGY

PHR: Project Narrative Eye injuries from exposure to the chemical warfare agent sulfur mustard can lead to severe blinding diseases. In response to NIH Chemical Countermeasures Research Program, we are proposing to to investigate the role of senescence after such injuries and to identify pathways for preventing/treating the severe blinding complications.

PI_NAMEs: DJALILIAN, ALI R (contact)

PROGRAM_OFFICER_NAME: ARAJ, HOUMAM H

PROJECT_TERMS: Ablation;Acute;aging related disease;angiogenesis;Apoptosis;Blindness;bone marrow mesenchymal stem cell;chemical countermeasure;chemical threat;Chemical Warfare Agents;chemotherapeutic agent;Chronic;Cicatrix;Cornea;Corneal Diseases;cytokine;Data;Development;Disease;DNA Damage;Dose;Endothelium;Environment;Epithelial Cells;epithelial wound;Epithelium;experience;Experimental Animal Model;Exposure to;Eye;Eye Injuries;Fibroblasts;Functional disorder;Genetic;Growth;Growth Factor;improved;Inflammation;Inflammatory;injured;Injury;Keratitis;Keratopathy;limbal;Mechlorethamine;Modeling;mouse model;Mus;Mustard;Mustard Gas;Necrosis;neovascularization;novel;novel strategies;ocular surface;Onset of illness;Oxidative Stress;Paracrine Communication;Pathologic;Pathway interactions;patient subsets;Patients;Peptide Hydrolases;Perforation;pharmacologic;Predisposition;prevent;Prevention;Process;programs;Publishing;Rattus;Reporting;Research;response;Role;senescence;senescence associated secretory phenotype;senescent cell;severe injury;Severities;Skin;stem cells;Testing;Tissues;Ulcer;United States National Institutes of Health;vapor;Vascularization;Vesicants;wound

PROJECT_TITLE: Pathophysiology of Chronic and Delayed Mustard Gas Keratopathy

STUDY_SECTION_NAME: Special Emphasis Panel[ZES1 LWJ-D (CA)]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Breast Cancer;Building Research Capacity at Institutions with Limited NIH Funding;Cancer;Natural Products;Women's Health Research

ORG_CITY: SAN ANTONIO

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF THE INCARNATE WORD

PHR: PROJECT NARRATIVE Triple-negative breast cancer is a heterogeneous and highly aggressive type of breast cancer with limited treatment options. This proposal seeks to elucidate the mechanism of action and define critical pharmacophores of activity in a novel compound with selective activity against a distinct TNBC subtype. Mechanistic knowledge obtained from this study will inform on oncogenic pathways that can be pharmacologically modulated to establish and generate a more effective targeted treatment for this disease.

PI_NAMEs: FERMAINTT, CHARLES STEVEN (contact)

PROGRAM_OFFICER_NAME: REVILLEZA, MARIA

PROJECT_TERMS: Advanced Development;Androgen Receptor;antagonist;Automobile Driving;Binding;Biochemical;Biological Assay;Biomedical Research;Breast Cancer Cell;Breast Cancer cell line;Breast Cancer Patient;cancer subtypes;Carbon;career;Cell Line;Cells;cellular targeting;Cessation of life;Chemicals;chemotherapy;Classification;Clustered Regularly Interspaced Short Palindromic Repeats;Companions;Cyclic AMP-Dependent Protein Kinases;cytotoxic;cytotoxicity;daphnane;Daphne plant;Development;Disease;Diterpenes;Enzymes;Epoxy Compounds;ERBB2 gene;Esters;Estrogens;Evaluation;Family;Fractionation;functional group;Future;improved;In Vitro;innovation;insight;Institution;Intervention;Isoenzymes;Knock-out;Knowledge;Malignant Breast Neoplasm;Measures;Mediating;member;Mentors;Mesenchymal;Molecular;Molecular Target;Natural Products;novel;Oncogenic;Pathway interactions;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacologic;Pharmacological Treatment;pharmacophore;Phosphotransferases;Progesterone;programs;Property;protein expression;Protein Kinase C;protein kinase C kinase;receptor;Research;Resistance;response;screening;Series;skeletal;Skeleton;Structure;targeted treatment;Testing;Training;treatment response;triple-negative invasive breast carcinoma;undergraduate student;United States;Woman;Work

PROJECT_TITLE: Mechanistic Evaluation of Macrocyclic Diterpenoids with Selective Triple Negative Breast Cancer Activity

STUDY_SECTION_NAME: Special Emphasis Panel[ZGM1 RCB-7 (SF)]


FUNDING_MECHANISM: RESEARCH CENTERS

ORG_CITY: IRVINE

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: IMPACT OF CANNABINOIDS ACROSS THE LIFESPAN (ICAL): NARRATIVE Teenagers use cannabis more than any other recreational substance. Sweeping changes in social attitudes and relaxed legal restrictions have highlighted a critical need for research that investigates in a rigorous manner the long-term consequences of adolescent cannabis use on brain function and mental health. ICAL addresses this fundamental gap in knowledge: as such, it has the potential not only to impact our understanding of adolescent health, but also to inform medical practice and public policy.

PI_NAMEs: PIOMELLI, DANIELE  (contact)

PROGRAM_OFFICER_NAME: LIN, YU

PROJECT_TERMS: Address;Adolescence;Adolescent;adolescent health;Adult;Affect;Affective;Animals;Attention;Attitude;Behavior;Behavioral;behavioral outcome;biobank;Biological Psychiatry;Brain;brain dysfunction;Cannabinoids;Cannabis;career;Cell Nucleus;Cellular Metabolic Process;Cognitive;cognitive ability;Communication;Communities;Complex;Consumption;Country;Cytometry;Data;density;design;Development;Drug Kinetics;Educational workshop;Electrophysiology (science);endocannabinoid signaling;endogenous cannabinoid system;Epidemiology;Episodic memory;Etiology;Evaluation;Event;Exposure to;Faculty;Female;Fostering;Funding;General Population;Goals;graduate student;Grant;Health Professional;high standard;Hippocampus;Homeostasis;Image;Immune;Impairment;Incidence;innovation;International;Intoxication;Journals;Knowledge;Laboratories;laboratory experiment;Legal;Life;life span;Link;male;marijuana use;Medical;Memory;Mental disorders;Mental Health;Metabolic;Metabolism;Methodology;Methods;Microglia;Mission;Modeling;Modification;Molecular;Mus;National Institute of Drug Abuse;Nature;neural;neurobehavioral;Neuronal Plasticity;Neurons;Neurosciences;Neurotransmitters;Opioid;Outcome;Participant;Pattern;Peer Review;Periodicals;Persons;Phenotype;Postdoctoral Fellow;Prefrontal Cortex;pressure;programs;Protocols documentation;Psychosocial Stress;Public Policy;Publications;Publishing;Rattus;Recreation;Recreational Drugs;Regimen;Relaxation;Reporting;Research;Research Personnel;Research Project Grants;response;Rewards;Risk;Route;Scientist;Services;sex;Signal Transduction;single nucleus RNA-sequencing;social;student mentoring;substance use;Surveys;symposium;Synapses;Synaptic plasticity;synergism;Techniques;Teenagers;Testing;Tetrahydrocannabinol;THC exposure;Time;Tissue Sample;Tissues;Training;training opportunity;transcriptome sequencing;Treatment Protocols;undergraduate student;Underrepresented Minority;webinar;Work

PROJECT_TITLE: Impact of Cannabinoid Across the Lifespan (ICAL)

STUDY_SECTION_NAME: Special Emphasis Panel[ZDA1 SXC-E (M1)]


NIH_SPENDING_CATS: Aging;Cannabinoid Research;Drug Abuse (NIDA only);Natural Products;Neurosciences;Substance Misuse

PROJECT_TERMS: Acceleration;addiction;Adolescence;Agreement;Anatomy;Animals;Behavior;Behavioral;Biochemistry;Budgets;Cannabinoids;Cannabis;Cognition;Communication;Communities;Complex;Disease;distinguished professor;Educational process of instructing;Educational workshop;endogenous cannabinoid system;Ensure;Equity;Event;Exposure to;Funding;Goals;graduate student;International;Leadership;life span;Location;Logistics;meetings;member;Mentors;Molecular;motivated behavior;National Institute of Drug Abuse;Neurobiology;Neurosciences;outreach;outreach program;Pharmacologic Substance;Postdoctoral Fellow;Process;professor;programs;Protocols documentation;Reporting;Research;Research Personnel;Research Project Grants;Resources;Schedule;Science;Signal Transduction;Specialist;Students;substance use;symposium;Synapses;Synaptic plasticity;System;Testing;Tetrahydrocannabinol;Training;Training Programs;undergraduate student;Underrepresented Minority;web site;webinar;Wood material


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Cannabinoid Research;Drug Abuse (NIDA only);Endocannabinoid System Research;Natural Products;Neurosciences;Pediatric;Substance Misuse

PI_NAMEs: JUNG, KWANG MOOK (contact)

PROJECT_TERMS: Adolescence;Adolescent;Adult;Affect;Animals;Behavioral;Biological;Brain;Cannabinoids;Cannabis;Cells;CNR1 gene;Cognition;Collaborations;Communities;Complex;Consumption;Data Analyses;Development;Drug Kinetics;drug metabolism;Electronic Mail;endocannabinoid signaling;endogenous cannabinoid system;Ensure;Enterobacteria phage P1 Cre recombinase;Equipment and supply inventories;experimental study;Exposure to;fatty acid amide hydrolase;Female;Freezing;Funding;Gene Modified;Human;Immune;indexing;International;intraperitoneal;Investigation;Laboratories;Life;life span;LoxP-flanked allele;male;marijuana use;Media Campaign;Metabolic;Modeling;Molecular;motivated behavior;Motivation;mouse development;Mus;mutant;National Institute of Drug Abuse;Nociception;Organ;Pattern;Periodicals;Peripheral;Pharmacodynamics;Phenotype;Physiological Processes;Pilot Projects;Preparation;Process;programs;Protocols documentation;public repository;Publishing;Rattus;Research;Research Personnel;Resources;response;Rodent;Sampling;Scientist;Services;sex;Signal Transduction;social media;Specimen;Standardization;Synapses;System;Teenagers;Testing;THC exposure;Tissue Banks;Tissues;Treatment Protocols;web site;Work


NIH_SPENDING_CATS: Aging;Cannabinoid Research;Drug Abuse (NIDA only);Endocannabinoid System Research;Natural Products;Substance Misuse

PI_NAMEs: AHMED, FAIZY  (contact)

PROJECT_TERMS: Adolescence;Adolescent;Adult;Analytical Chemistry;anandamide;Animals;Architecture;Behavior;Behavioral;Biocompatible Materials;Biological Assay;cannabinoid drug;Cannabinoids;Cognition;Drug Kinetics;drug metabolism;Endocannabinoids;endogenous cannabinoid system;Epigenetic Process;Equipment;experience;Exposure to;Funding;Genetic Processes;graduate student;Human;innovation;instrumentation;life span;Lipids;Liquid Chromatography;Long-Term Effects;Maintenance;marijuana use;Methods;Molecular;Molecular Structure;motivated behavior;Mus;National Institute of Drug Abuse;Neuroanatomy;Neuronal Plasticity;novel;novel strategies;pharmacokinetics and pharmacodynamics;Postdoctoral Fellow;Preparation;Process;Property;Publications;Rattus;Sampling;Schedule;Series;sex;Synapses;synaptic function;System;tandem mass spectrometry;Teenagers;Testing;Tetrahydrocannabinol;Tissues;Training;Treatment Protocols


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Cannabinoid Research;Drug Abuse (NIDA only);Natural Products;Neurosciences;Substance Misuse

PI_NAMEs: GALL, CHRISTINE M (contact)

PROJECT_TERMS: addiction;Adolescence;Anatomy;Applications Grants;Architecture;Area;Behavior;Behavioral;Brain;California;Cannabinoids;Cannabis;career;career development;Cognition;Communities;Consultations;Department chair;early life exposure;endogenous cannabinoid system;Epigenetic Process;Exposure to;extracellular vesicles;Faculty;Female;Fostering;Funding;Genetic Processes;Individual;innovation;Leadership;life span;male;member;Mentors;Mentorship;Mission;Molecular;Molecular Structure;motivated behavior;Motivation;Mus;National Institute of Drug Abuse;Neuroanatomy;Neurobiology;Neurosciences;Pilot Projects;Preparation;Process;professor;programs;Publishing;Rattus;recruit;reproductive function;Research;Research Personnel;Resources;Rewards;senior faculty;sex;Signal Transduction;Synapses;synaptic function;synergism;System;Testing;Tetrahydrocannabinol;Tissue Banks;Training;Work


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Cannabinoid Research;Drug Abuse (NIDA only);Endocannabinoid System Research;Genetics;Natural Products;Neurosciences;Pediatric;Substance Misuse

PROJECT_TERMS: Ablation;Acceleration;Adolescence;Adolescent;adolescent substance use;Affect;antagonist;Attention;base;Behavior;Behavioral;brain dysfunction;Brain region;cannabinoid receptor antagonist;Cannabinoids;Cannabis;cell type;Cells;CNR1 gene;Cognition;cognitive ability;Collaborations;Complex;Cytometry;Data Analyses;Data Set;density;Development;Electrophysiology (science);endocannabinoid signaling;Endocannabinoids;endogenous cannabinoid system;Environment;Enzymes;epidemiologic data;epidemiology study;Epigenetic Process;Episodic memory;Etiology;Event;Exhibits;experimental study;Exposure to;fatty acid amide hydrolase;Female;Fostering;Foundations;Functional disorder;Funding;Gene Deletion;Genetic;Genetic Transcription;Goals;Health;health assessment;Hippocampus;Homeostasis;Host Defense;Image;Impairment;Incidence;Infection;laboratory experiment;life span;Link;Long-Term Potentiation;male;marijuana use;Mediating;Medicine;Memory;Mental disorders;microbial;Microglia;Molecular;Morphology;motivated behavior;Mus;National Institute of Drug Abuse;Nature;neural;neurobehavioral;Neuronal Plasticity;Neurons;Neurotransmitters;Opioid;Outcome;Pharmaceutical Preparations;pharmacologic;Prefrontal Cortex;prevent;Process;programs;Property;Psychosocial Stress;Rattus;receptor;Reporting;Research;Research Activity;response;Rewards;Risk;Route;Series;sex;Signal Transduction;single nucleus RNA-sequencing;social stress;Structure;substance use;Synapses;Synaptic plasticity;System;Techniques;Teenagers;Testing;Tetrahydrocannabinol;THC exposure;Time


NIH_SPENDING_CATS: Cannabinoid Research;Drug Abuse (NIDA only);Endocannabinoid System Research;Estrogen;Natural Products;Neurosciences;Pediatric;Substance Misuse;Women's Health Research

PROJECT_TERMS: 2-arachidonylglycerol;Ablation;Actins;Adolescence;Adolescent;Adult;Affect;Age;age related;antagonist;base;Behavioral;Cannabinoids;cell type;Cells;CNR1 gene;cognitive function;conditional knockout;Cytoskeleton;dentate gyrus;Development;early adolescence;Elements;Endocannabinoids;Engineering;Episodic memory;estrogen disruption;Estrogen Receptors;Estrogens;Excision;Excitatory Synapse;Exposure to;F-Actin;fatty acid amide hydrolase;Female;Fluorescence;Functional disorder;Genetic;Goals;Hippocampus;Impairment;Individual;Knockout Mice;Lateral;Learning;life span;Link;Long-Term Potentiation;Macrophage Colony-Stimulating Factor Receptor;male;marijuana use;Mediating;Memory;Memory impairment;Microglia;Molecular;Mus;Mutant Strains Mice;Neurobiology;novel;Pattern;Perforant Pathway;Pharmaceutical Preparations;pharmacologic;Population;prevent;Process;programs;Proteins;Rattus;Receptor Activation;Receptor Signaling;Research;response;Rodent;Role;sex;Sex Differences;sexual dimorphism;Signal Transduction;stem cells;Synapses;Synaptic plasticity;System;Testing;THC exposure;tomography;treatment strategy;Vertebral column;Work


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cannabinoid Research;Drug Abuse (NIDA only);Natural Products;Neurosciences;Opioid Misuse and Addiction;Opioids;Pediatric;Substance Misuse

PI_NAMEs: MAHLER, STEPHEN VINCENT (contact)


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Data Science;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_CITY: East Lansing

ORG_NAME: ATTMOS INC.

PHR: Project Narrative We will create and deploy a novel workflow tool to address the prediction of protein ligand binding free energies. The resulting computer program will impact our ability to reliably and routinely identify drug-like molecules that could be useful in the treatment of a number of diseases.

PI_NAMEs: MANATHUNGA, MADUSHANKA  (contact)

PROGRAM_OFFICER_NAME: NGUYEN, HAN

PROJECT_TERMS: Address;Adoption;Binding;Binding Proteins;Biochemical;Biotechnology;Clinical Trials;cloud based;Code;Collaborations;Communities;Complex;computer infrastructure;computer program;Computer software;Computers;Computing Methodologies;cost;Data;Data Set;Databases;Development;Disease;drug candidate;drug development;drug discovery;drug-like compound;Engineering;Ensure;experimental study;Feedback;flexibility;Free Energy;Generations;Goals;improved;in silico;Industrialization;Infrastructure;interest;intermolecular interaction;Intuition;lead optimization;Letters;Ligands;Literature;Machine Learning;Marketing;Measures;mechanical force;Methodology;Methods;Modeling;molecular dynamics;molecular mechanics;Names;novel;novel therapeutics;Online Systems;Performance;Pharmaceutical Preparations;Pharmacologic Substance;Phase;phase 2 study;Play;Positioning Attribute;Process;prospective;Proteins;Publications;Publishing;Reporting;Research;Role;Running;Scanning;Scientist;Series;Side;simulation;Small Business Innovation Research Grant;Software Tools;Specificity;Structure;Surveys;System;Technology;Testing;Thermodynamics;tool;training data;user-friendly;Validation;Work

PROJECT_TITLE: Computational Infrastructure for Automated Force Field Development and Optimization


NIH_SPENDING_CATS: Biotechnology

ORG_CITY: Raleigh

ORG_NAME: GLYCAN THERAPEUTICS CORPORATION

ORG_STATE: NC

PHR: Project Narrative Heparan sulfate have many important biological functions. The overall goals of this project are to synthesize and commercialize a large library of heparan sulfate like hexasaccharide mimetics, providing enabling tools to enhance the understanding of their biological properties and the development of novel therapeutics against important human diseases.

PI_NAMEs: SU, GUOWEI  (contact)

PROGRAM_OFFICER_NAME: ASLAN, KADIR

PROJECT_TITLE: Synthesis of the library of heparan sulfate hexasaccharide mimetics


ADMINISTERING_IC: OH

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH

ORG_CITY: ANN ARBOR

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: PROJECT NARRATIVE PUBLIC HEALTH RELEVANCE: Nail salon workers represent low-wage, underinsured, immigrant women in the services sector of the U.S. workforce whose occupational health and safety needs are overlooked and understudied. Prior to the COVID-19 pandemic, this small business industry faced a number of workplace hazards; these workers’ vulnerability has been worsened by the pandemic but the current state of their occupational health and safety needs, as well as their wellbeing is unknown. Results from the proposed study are directly relevant to the Services Sector and Healthy Work Design and Well-Being Cross-Sector at the National Institute for Occupational Safety and Health (NIOSH).

PI_NAMEs: ROSEMBERG, MARIE-ANNE SANON (contact)

PROJECT_TITLE: COVID-19 and Nail Salon Workers: Taking Stock of the Pandemic's Impact on Occupational Health and Safety

STUDY_SECTION: SOH

STUDY_SECTION_NAME: Safety and Occupational Health Study Section[SOH]


NIH_SPENDING_CATS: Data Science;Genetics;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_CITY: UNIVERSITY PARK

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

ORG_STATE: PA

PHR: Narrative statement Synonymous mutations, which change the rate at which a codon position is translated by the ribosome but not the amino acid it encodes, can alter protein structure and function, affect mRNA half-lives, and contribute to disease. Molecular modeling, interpretable machine learning, and synthesizing big biological datasets are suggesting molecular mechanisms that can connect this class of mutations to these outcomes. This research proposal will utilize these tools and experimental methods to gain quantitative molecular insights into these phenomena.

PI_NAMEs: O'BRIEN, EDWARD PATRICK (contact)

PROGRAM_OFFICER_NAME: CHO, THOMAS Y

PROJECT_TERMS: Affect;Amino Acids;Bacteria;Big Data;Binding;Bioinformatics;Biological;Catalysis;cell growth;Cells;Chemotaxis;Circadian Rhythms;Codon Nucleotides;computerized tools;Cryoelectron Microscopy;Data;Data Set;Disease;DNA;Drosophila genus;enzyme activity;Enzymes;explainable machine learning;follow-up;fungus;Gene Expression;Genetic Transcription;Growth;Human;in silico;in vivo evaluation;insight;Kinetics;Lead;Link;Machine Learning;Malignant Neoplasms;Mass Spectrum Analysis;Messenger RNA;Methods;migration;Molecular;molecular modeling;mRNA Transcript Degradation;Mutation;novel;NUP214 gene;Outcome;Pattern;Phenotype;Positioning Attribute;predictive modeling;Process;promoter;protein function;protein misfolding;protein structure;Proteins;rate of change;Research;Research Proposals;Ribosomes;simulation;Statistical Methods;Techniques;Testing;theories;Time;tool;transcription factor;Translating;Translations

PROJECT_TITLE: Translation Kinetics and their Effects on Protein Structure and Function, mRNA half-lives, and Cellular Phenotype

STUDY_SECTION: MRAB

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


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Autoimmune Disease;Digestive Diseases;Immunotherapy;Inflammatory Bowel Disease;Precision Medicine;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: PROJECT NARRATIVE  Inflammatory bowel disease (IBD) is highly prevalent with a significant lifetime morbidity and financial burden on society. A better understanding of the factors that drive IBD epithelial repair will help to improve mucosal healing and long-term disease remission. Understanding how intestinal stem cells adapt their energy profile to drive their repairing function to heal the damaged tissue will enhance our overall understanding of IBD and may open the door to biomarker discovery and novel treatment strategies.

PI_NAMEs: MENTRUP, HEATHER  (contact)

PROGRAM_OFFICER_NAME: DENSMORE, CHRISTINE L

PROJECT_TERMS: 3-Dimensional;Atrophic;Bioenergetics;Biological Models;biomarker discovery;biomarker identification;Bone Marrow;Cell Proliferation;Cells;Cellular Metabolic Process;Chronic;cohort;Colitis;Complex;cost;Coupled;Crohn's disease;Deoxyglucose;design;Development;Disease;Disease remission;Energy Supply;Environment;Epithelial Cells;epithelial injury;epithelial repair;Epithelium;epithelium regeneration;experience;Exposure to;fetal;Financial Hardship;Frequencies;Genus Hippocampus;Glucose;glucose transport;Glucose Transporter;Glycolysis;Glycolysis Inhibition;Goals;Grant;healing;Health;Histologic;Homeostasis;Human;Immune;Immune response;immunomodulatory therapies;immunoregulation;Immunotherapy;Impairment;improved;Individual;Inflammation;Inflammatory Bowel Diseases;Injury;injury and repair;intestinal epithelium;intestinal injury;Intestines;LGR5 gene;Macrophage;Mass Spectrum Analysis;Messenger RNA;Metabolic;metabolic profile;Metabolism;metabolome;metabolomics;Modeling;Molecular;molecular phenotype;Morbidity - disease rate;Morphology;Mucous Membrane;Mus;Natural regeneration;novel;novel marker;novel therapeutic intervention;novel therapeutics;Organoids;Output;Patients;Pediatric Hospitals;Pharmaceutical Preparations;Phenotype;Play;Population;Process;Production;Proliferating;Radiation;Recovery;Recurrence;regenerative;Regenerative response;Relapse;relapse patients;repair function;repair model;repaired;reparative capacity;Reporter;Research;Research Personnel;Resolution;Resources;response;Role;self-renewal;SLC2A1 gene;Societies;Sodium Dextran Sulfate;stem cell biomarkers;stem cell function;stem cell population;stem cells;Structure;success;Surface;System;Tamoxifen;targeted treatment;Therapeutic Intervention;tissue repair;Tissues;Training;treatment strategy;Ulcerative Colitis;United States;Universities;Up-Regulation;Work

PROJECT_TITLE: Intestinal Stem Cell Metabolism in Inflammatory Bowel Disease Mucosal Healing


ED_INST_TYPE: SCHOOLS OF SOCIAL WELFARE/WORK

NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Rural Health;Social Determinants of Health

ORG_CITY: SAINT LOUIS

ORG_DEPT: SOCIAL SCIENCES

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE This study is relevant to public health because it addresses the limited knowledge about the roles of support system and the contextually specific socioeconomic influence on physical and psychological health of older adults in a low resource setting of rural Cambodia. Findings can be used by health interventionists and researchers to compare public health interventions focused on providing tangible resources against ones focused on improving self-image and the sense of economic fulfillment. Because this study will add to the small body of aging and public health literature about older Cambodians, the long-term goal is for aging researchers to use the findings to advance conceptual and empirical work in this country and other low- and middle-income countries, thus advancing the mission of the NIA to support social and economic research on aging around the world and to increase diversity in research among underrepresented population. 1

PI_NAMEs: KUY, KAKADA  (contact)

PROGRAM_OFFICER_NAME: TORRES, DELANY

PROJECT_TERMS: Address;Age;aged;Aging;aging population;Asian;Cambodia;Cambodian;Characteristics;Child;Communities;community intervention;comparison intervention;Conflict (Psychology);Country;Data;Dependence;Development;Disparity;disparity reduction;economic indicator;Economics;Educational Status;Emotional;Equation;Family;Friends;Gender;General Population;Goals;Government;Health;health determinants;Health Status;Household;improved;Income;indexing;Individual;Infrastructure;International;Intervention;Investigation;Knowledge;Life Cycle Stages;Literature;low and middle-income countries;Marital Status;Measurement;Measures;Mediating;Mediation;Mental Health;Mission;Modeling;older adult;Older Population;Outcome;Personal Satisfaction;physical conditioning;Policies;Policy Developments;Population;Positioning Attribute;Program Development;Province;psychological distress;Public Health;public health intervention;Publications;Publishing;Recording of previous events;Research;Research Personnel;Resource-limited setting;Resources;response;Role;Rural;rural area;rural dwellers;rural residence;rural setting;Self Perception;social;Social Network;Social support;Social Welfare;Socioeconomic Factors;Socioeconomic Status;socioeconomics;Southeastern Asia;Support System;Surveys;Underrepresented Populations;United Nations;Violence;welfare assistance;Well in self;Work

PROJECT_TITLE: Socioeconomic Determinants of Health and Well-Being in a Low Resource Setting: A Case of Older Adults Living in a Rural Setting in the Northwestern Cambodia

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development for Established Investigators and Conference Grants Study Section[AGCD-4]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Radiation Oncology

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: PROJECT NARRATIVE Novel, effective, targeted strategies for both earlier detection and treatment of metastatic cancers could greatly improve patient outcomes. With the identification of αvβ6, a molecule that is on many cancers and is linked to a poor survival rate for patients, and the development of our promising theranostic pair that target the αvβ6, we now have the opportunity to develop these targeted strategies. In this application we propose a clinical trial to test our theranostic pair to determine if it is effective in patients with metastatic carcinoma.

PI_NAMEs: FOSTER, CAMERON CARL;SUTCLIFFE, JULIE L (contact)

PROGRAM_OFFICER_NAME: CAPALA, JACEK

PROJECT_TERMS: absorption;Adult;advanced disease;Affinity;Aftercare;Anterior;Binding;Biodistribution;Biological Assay;Blood;Blood specimen;bone;Bone Marrow;Brain;cancer imaging;cancer therapy;cancer type;Carcinoma;Cardiotoxicity;Cell Surface Receptors;Cells;Clinical;clinical care;Clinical Data;Clinical Research;clinical translation;Clinical Trials;Collaborations;Cyclic GMP;Detection;Development;Diagnostic;Discipline of Nuclear Medicine;Disease;Disseminated Malignant Neoplasm;Distant;Dose;dosimetry;Drug Kinetics;Early Diagnosis;Early treatment;efficacy evaluation;Eligibility Determination;Epithelium;Evaluation;Excretory function;follow-up;Fostering;Goals;Hematology;Hepatobiliary;Hour;Image;Image Analysis;improved;In Vitro;in vivo;Infusion procedures;Injections;Integrins;interest;intravenous injection;Invaded;Kidney;Laboratories;Lesion;Link;Liver;Lung;Malignant Neoplasms;Metastatic Carcinoma;Molecular Target;mouse model;nanomolar;Neoplasm Metastasis;Non-Invasive Detection;novel;Oncology;Organ;Outcome;participant enrollment;Patient-Focused Outcomes;Patients;Peptides;PET/CT scan;phase II trial;Positron-Emission Tomography;preclinical study;Prevalence;Primary Neoplasm;primary outcome;Process;Property;prospective;Prospective Studies;Radiation Oncology;Radiation therapy;Radiochemistry;Radiopharmaceuticals;receptor;Research;Resources;Role;Safety;Schedule;single photon emission computed tomography;Site;Skeleton;Specificity;Speed;standard of care;Survival Rate;Testing;theranostics;Therapeutic;Time;Toxic effect;Translating;Translational Research;Translations;Treatment Efficacy;treatment response;Tumor stage;uptake;X-Ray Computed Tomography

PROJECT_TITLE: A novel molecularly targeted theranostic approach via the alphavbeta6 integrin for the detection and treatment of metastatic cancers

STUDY_SECTION: CTIS

STUDY_SECTION_NAME: Clinical Translational Imaging Science Study Section[CTIS]


PHR: PROJECT NARRATIVE Using azide-containing hypervalent iodine reagents, we have developed a novel chemoproteomic platform termed Protein Surface Azidation Mass Spectrometry (ProSurA-MS) that detects conformational changes on protein surface with unbiased chemoselectivity. Combined with bioorthogonal chemistry, ProSurA-MS effectively mapped dynamics of purified proteins upon denaturation, protein-small molecule interaction, and protein-protein interaction, conformational changes of a zinc-binding protein in whole cell lysate upon zinc depletion, and measured proteome-wide azidation in live cells, thus potentiating the characterization of protein dynamics in complex biological environments. The herein proposed studies will enable characterization of dynamic changes in protein conformation induced by post-translational modifications and metal binding, basic understanding of the chemical mechanism behind the ProSurA reaction and development of second generation reagents with greater azidation yield and surface coverage, and investigation of protein interaction networks via unbiased crosslinking.

PI_NAMEs: ADIBEKIAN, ALEXANDER  (contact)

PROGRAM_OFFICER_NAME: BARNES, CHARLES ASHLEY

PROJECT_TERMS: Acetylation;Amino Acids;aqueous;Azides;Binding;Biological;biophysical tools;Biophysics;Buffers;Cells;Chemicals;Chemistry;chemoproteomics;Co-Immunoprecipitations;Complex;Coupled;crosslink;Cysteine;design;detection method;Development;Disease;disulfide bond;endopeptidase Clp;Ensure;Environment;Enzymes;Equipment;Generations;genetic variant;Housekeeping;improved;interest;Investigation;Iodine;Ion Transport;Maps;Mass Spectrum Analysis;Measures;Mediating;Membrane Proteins;Metals;Methods;Modeling;Molecular Conformation;Monitor;novel;Oxidative Regulation;Oxidative Stress;Peptides;Phosphines;Post-Translational Protein Processing;Preparation;Protein Conformation;Protein Dynamics;protein profiling;protein protein interaction;protein purification;protein structure;Proteins;Proteome;Reaction;Reagent;Reporting;Reproducibility;response;Sampling;Site;small molecule;Solubility;Special Equipment;Surface;synthetic peptide;System;Techniques;Technology;Testing;tool;Zinc;zinc-binding protein

PROJECT_TITLE: Probing conformational changes by protein surface azidation

STUDY_SECTION: MSFB

STUDY_SECTION_NAME: Macromolecular Structure and Function B Study Section[MSFB]


ADMINISTERING_IC: HD

ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

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

NIH_SPENDING_CATS: Chronic Pain;Clinical Research;Neurosciences;Pain Research;Vulvodynia;Women's Health Research

ORG_CITY: ROCHESTER

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: PROJECT NARRATIVE Localized provoked vulvodynia (LPV) is a common cause of painful intercourse in women of reproductive age, but therapy options short of surgery are limited and marginally effective and patients may suffer for months to years before finding relief, if ever. We have identified new targets for LPV therapy that are likely involved in other pain conditions and that could lead to a breakthrough in analgesic therapy. In the wake of the opioid epidemic, it is imperative that we develop new, effective, and safe pain therapies to replace current medications that result in dependence.

PI_NAMEs: WOOD, MEGAN LINDSAY FALSETTA (contact)

PROGRAM_OFFICER_NAME: AHN, HELENA HYESOOK

PROJECT_TERMS: 3-Dimensional;Absence of pain sensation;Age;Agonist;allodynia;Analgesics;antagonist;Area;Biological Assay;Biopsy;capsaicin receptor;Cell Fractionation;Cells;Chronic;chronic painful condition;Clinical;Complement Factor B;cytokine;Data;dectin 1;Dependence;design;Dinoprostone;Disease;Drug Addiction;drug development;Dyspareunia;Enzyme-Linked Immunosorbent Assay;Evaluation;Family;Fibroblasts;Genetic Transcription;Goals;Healthcare;Host Defense;Human;human tissue;Hyperalgesia;Hyperthermia;Immune;Immunohistochemistry;Impairment;improved;in vivo;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Response;innovation;Interleukin-6;Intervention;Libraries;Light;Link;Lipids;Luciferases;Mass Spectrum Analysis;Measures;Mediating;Mediator;member;Methods;Mission;Modeling;Mus;National Institute of Child Health and Human Development;National Institute of Drug Abuse;new therapeutic target;Nociception;novel therapeutics;Nuclear;Operative Surgical Procedures;Opiate Addiction;opioid epidemic;Pain;Pain management;Pain Measurement;pain symptom;Pain Threshold;Painless;PAR-2 Receptor;Pathway interactions;Patients;Perception;Persistent pain;Pharmaceutical Preparations;Play;Premenopause;prevent;Process;Production;Quality of life;Quantitative Reverse Transcriptase PCR;receptor;release of sequestered calcium ion into cytoplasm;Reporter;Reproducibility;reproductive;response;Risk;Role;Sensory;Serotonin;sexual relationship;Signal Pathway;Signal Transduction;Site;Small Interfering RNA;Stimulus;Syndrome;Tampons;targeted treatment;Techniques;Temperature;therapeutic candidate;therapeutic development;Therapeutic Intervention;therapeutic target;therapeutically effective;tissue culture;Tissues;Topical application;Touch sensation;United States National Institutes of Health;Vagina;Vestibule;Vulva;vulvar pain;Vulvodynia;Walking;Western Blotting;Woman;Women's Health

PROJECT_TITLE: Transient Vanilloid Receptors and Vulvar Pain: New Therapeutic Targets for Vulvodynia

STUDY_SECTION: ICER

STUDY_SECTION_NAME: Integrative and Clinical Endocrinology and Reproduction Study Section[ICER]


NIH_SPENDING_CATS: Aging;Bioengineering;Cancer;Clinical Research;Colorectal Cancer;Digestive Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Hematology;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Precision Medicine;Prevention;Prostate Cancer;Racial and Ethnic Minority Health Research;Rare Diseases;Social Determinants of Health;Urologic Diseases

ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: PROJECT NARRATIVE Algorithmic bias is an emerging and highly relevant topic in health policy that draws attention to the idea that seemingly well-performing predictive algorithms built using biased data can propagate systemic biases and disparities existing in clinical practice. Disparities along the cancer care continuum from diagnosis to survivorship can lead to distorted risk predictions; using these for decision-making may propagate and exacerbate biases that exist in clinical practice and result in poorer outcomes for certain subgroups. The major goal of this project is to understand and address algorithmic bias in the personalized risk-adaptive surveillance (PRAISE) framework developed and applied to colorectal cancer in the parent grant, and to assess the implications of using a biased versus a bias-corrected algorithm to guide surveillance testing among colorectal cancer survivors. This important work will motivate the use of new methods for addressing bias in risk predictions in cancer and other clinical areas.

PI_NAMEs: BANSAL, AASTHAA  (contact)

PROGRAM_OFFICER_NAME: MITCHELL, SANDRA A

PROJECT_TERMS: Address;algorithmic bias;Algorithms;Area;Attention;Biological Markers;cancer care;cancer recurrence;Cancer Survivor;cancer survivorship care;Chronic Myeloid Leukemia;Clinic Visits;Clinical;Clinical Management;clinical practice;Cohort Studies;Collaborations;Collection;Colorectal Cancer;colorectal cancer screening;comparative effectiveness;Complex;Continuity of Patient Care;cost;cost outcomes;Coupling;Data;Decision Making;decision making algorithm;Decision Theory;Detection;Diagnosis;Disease Progression;Disease remission;Disparity;ethnic bias;ethnic disparity;Ethnic Population;Face;follow-up;Frequencies;Future;Goals;Guidelines;Health;Health Policy;Heterogeneity;high risk;improved;Individual;individual patient;innovation;Intuition;Life Expectancy;Long-Term Survivors;Machine Learning;Malignant neoplasm of lung;Malignant neoplasm of ovary;Malignant neoplasm of prostate;Malignant Neoplasms;Measurement;men;Methodology;Methods;Modeling;models and simulation;Monitor;Monitoring for Recurrence;Morbidity - disease rate;mortality;novel;Outcome;parent grant;patient subsets;Patient-Focused Outcomes;Patients;Pattern;Performance;personalized decision;Policies;prediction algorithm;predictive modeling;Race;racial disparity;Recommendation;Recurrence;Recurrent disease;Research;Risk;risk prediction;risk prediction model;Schedule;simulation;Source;Subgroup;surveillance strategy;survivorship;Testing;Time;Uncertainty;unnecessary treatment;Update;Work

PROJECT_TITLE: Personalized Risk-AdaptIve Surveillance (PRAISE) - Implications of Algorithmic Bias


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Immunotherapy;Neurosciences;Rare Diseases

ORG_CITY: DURHAM

ORG_DEPT: NEUROSURGERY

ORG_NAME: DUKE UNIVERSITY

PHR: Glioblastoma (GBM) is defined by a deeply immunosuppressive immune infiltrate implicated in intrinsic T cell ignorance and hindrance of systemic immunotherapy with immune checkpoint blockade. This project will unravel the mechanisms of local GBM immunotherapy with recombinant poliovirus, PVSRIPO, based on its uniquely broad and profound proinflammatory effects in the GBM myeloid infiltrate and surrounding brain. This project will define new therapy paradigms for viral GBM immunotherapy by addressing recently discovered factors in immunotherapy resistance.

PI_NAMEs: GROMEIER, MATTHIAS  (contact);NAIR, SMITA K.

PROGRAM_OFFICER_NAME: KOTLIAROVA, SVETLANA

PROJECT_TERMS: Acute;Address;Agonist;Antigens;attenuation;Automobile Driving;Biological;Brain;Brain Neoplasms;brain parenchyma;cancer cell;cancer immunotherapy;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;cell killing;Cells;Cellular Infiltrate;Clinic;Clinical;constitutive expression;Cross Presentation;Dendritic Cells;Dose;Double-Stranded RNA;effector T cell;Engineering;Event;experience;Family Picornaviridae;Functional disorder;Funding;Glioblastoma;Glioma;Goals;Heterogeneity;Human;Human poliovirus;Immune;immune cell infiltrate;immune checkpoint blockade;Immunity;Immunobiology;Immunologic Surveillance;Immunologics;Immunosuppression;Immunotherapy;imprint;improved;Induced Neurons;Infection;Infiltration;Inflammation;Inflammatory;Inflammatory Response;insight;Institution;Interferon Type I;Interferons;Internal Ribosome Entry Site;Investigation;Ligation;Lytic;Macrophage;Malignant Glioma;Malignant Neoplasms;Mediating;Mediator;Microglia;Modeling;Mononuclear;Mus;Mutation;Myelogenous;Myeloid Cells;Neoplasms;neoplastic cell;neuroinflammation;neurotropic;neurotropic virus;Newly Diagnosed;Non-Malignant;novel therapeutics;Outcome;patient subsets;Patients;Pattern;Pattern recognition receptor;Phagocytes;Phenotype;Physiological;polarized cell;Poliomyelitis;poliovirus receptor;premature;prevent;programs;Proliferating;radiological imaging;receptor;Recombinants;Recurrence;release factor 3;Research;Resistance;Resolution;response;Rhinovirus;RNA Viruses;Role;sensor;Shapes;Signal Transduction;Slice;stem;success;Syndrome;System;T cell infiltration;T-Lymphocyte;targeted treatment;Testing;Time;Tissues;TNFRSF5 gene;trait;tumor;Tumor Antigens;Tumor Immunity;tumor microenvironment;tumor progression;Tumor Promotion;Viral;Virotherapy;Virus;Virus Replication;Work

PROJECT_TITLE: Innate Antiviral Signals for Cancer Immunotherapy

STUDY_SECTION: CNBT

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


ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: Project Relevance Cholesterol serves as a precursor molecule for the biosynthesis of steroid hormones, bile acids, and vitamin D, and plays a role as a Hedgehog signal transducer. In this project, we will employ cell biological and structural approaches to study the membrane proteins involved in cholesterol signaling, biosynthesis, and storage. Completion of the proposed studies will not only provide insight into the mechanisms underlying HH signal transduction and cholesterol metabolism but will also reduce the incidence of cardiovascular disease and cancers.

PI_NAMEs: LI, XIAOCHUN  (contact)

PROGRAM_OFFICER_NAME: TAYLOR, VERONICA

PROJECT_TERMS: Acetyl Coenzyme A;acyl group;Adult;Anabolism;Atherosclerosis;Bile Acids;Binding;Biological;Blood;Cardiovascular Diseases;Cells;Cholesterol;cholesterol biosynthesis;Cholesterol Esters;Cholesterol Homeostasis;Coenzyme A;Complex;Cryoelectron Microscopy;Embryonic Development;Endoplasmic Reticulum;Enzymes;Erinaceidae;Growth;hedgehog signal transduction;Homeostasis;Human;Incidence;insight;Intestines;Investigation;Lanosterol;LDL Cholesterol Lipoproteins;Ligands;Ligase;Lipids;Lipoproteins;Liver;Maintenance;Malignant Neoplasms;Mammalian Cell;Mediating;Membrane;Membrane Proteins;Metabolism;Methods;Mevalonic Acid;Molecular;novel;Oxidoreductase;Pathway interactions;Permeability;Pharmaceutical Preparations;pharmacologic;Plasma;Play;prevent;Reaction;Regulation;Role;Series;Signal Transduction;small molecule;smoothened signaling pathway;steroid hormone biosynthesis;Sterol O-Acyltransferase;sterol O-acyltransferase 1;sterol O-acyltransferase 2;Sterols;Structure;synthetic enzyme;Tissues;trafficking;Transducers;tumorigenesis;ubiquitin-protein ligase;Vitamin D;Work

PROJECT_TITLE: Structural and Functional Investigations on Cholesterol Signaling and Metabolism


NIH_SPENDING_CATS: Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Contraception/Reproduction;Endometriosis;Neurosciences;Pain Research;Women's Health Research

PHR: Project Narrative Treating pelvic pain remains a significant challenge as current treatment strategies are dependent on our limited understanding of the underlying mechanisms that promote pain. Findings from the proposed clinical trial will help clinicians and researchers better understand the impact of pelvic and systemic inflammation on central nervous system sensitization, and how these pathways are affected by hormonal suppression. These results will have broad implications for understanding the neurobiological mechanisms through which hormonal suppression produces pain relief in many women with pelvic pain.

PI_NAMEs: AS-SANIE, SAWSAN  (contact);SCHREPF, ANDREW

PROJECT_TERMS: Affect;Aftercare;Analgesics;antagonist;associated symptom;Attenuated;Biology;Brain;Central Nervous System;central sensitization;Chronic pain syndrome;chronic pelvic pain;Clinical;clinical phenotype;clinical practice;Clinical Trials;comorbidity;Complex;cost;Data;Disease;disease model;Disproportionately impacts women;dosage;Dose;Double-Blind Method;Economics;endometriosis;Estradiol;Estrogens;Evaluation;experience;Fatigue;FDA approved;Functional Magnetic Resonance Imaging;Gonadotropin-Releasing Hormone Receptor;Gynecologic;Hormonal;Hormones;Hypersensitivity;Hysterectomy;improved;Inflammation;Inflammatory;Interstitial Cystitis;Intervention;Irritable Bowel Syndrome;Lesion;Measures;Mediating;Medical;Migraine;neurobiological mechanism;Neurobiology;Outcome;Pain;pain model;pain relief;Pathway interactions;Patients;Pelvic Pain;Pelvis;Peripheral;Pharmaceutical Preparations;Phenotype;Placebos;Positioning Attribute;predicting response;Randomized;randomized placebo-controlled clinical trial;randomized, clinical trials;recruit;Reproductive Biology;Research Personnel;response;Risk Factors;Severities;Severity of illness;Stimulus;Symptoms;systemic inflammatory response;Testing;treatment effect;Treatment outcome;treatment strategy;United States;Vulnerable Populations;Woman;Work

PROJECT_TITLE: The impact of hormonal modulation on systemic inflammation and central sensitization


NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurosciences;Physical Activity;Physical Injury - Accidents and Adverse Effects;Physical Rehabilitation;Regenerative Medicine;Rehabilitation;Spinal Cord Injury;Traumatic Head and Spine Injury

ORG_CITY: PISCATAWAY

ORG_DEPT: NEUROSCIENCES

ORG_NAME: RUTGERS, THE STATE UNIV OF N.J.

ORG_STATE: NJ

PHR: PROJECT NARRATIVE Sensory-based rehabilitation following spinal cord injury (SCI) facilitates neural rewiring for functional recovery, but it is unknown if different sensory-based training programs, such as forced exercise therapy and non-forced exercise, give rise to different rewiring strategies and behavioral outcomes. The proposed research will characterize the neural rewiring strategies that occur in forced and non-forced exercise and elucidate contributions of paradoxical training paradigms to motor performance and recovery. With a unique combination of techniques and expertise of my mentors, my research will break down current barriers of translational preclinical research with the aim of instructing rehabilitation programs for SCI patients with the intent to maximize recovery.

PI_NAMEs: EISDORFER, JACLYN T. (contact)

PROGRAM_OFFICER_NAME: KIM, JENNY LILY

PROJECT_TERMS: Affect;Afferent Neurons;Anatomy;Animals;Artificial Intelligence;Award;Behavior;Behavioral;behavioral outcome;Biometry;Brain;career;career development;Clinic;Clinical;clinical translation;combinatorial;Complex;Computational Technique;Computer Vision Systems;Cues;Data Analyses;design;dorsal horn;Exercise;Exercise Therapy;exercise training;Fellowship;Fostering;functional improvement;Funding;genetic approach;Goals;Histologic;Human;Implanted Electrodes;improved;Injury;Interneurons;Joints;Knowledge;Label;Learning;Leg;Machine Learning;machine learning model;Maps;Mediating;Mentors;Mentorship;Mission;model building;Modeling;Motor;motor behavior;Motor Neurons;motor recovery;mouse genetics;Movement;Muscle;National Institute of Neurological Disorders and Stroke;neural;neural circuit;Neuronal Plasticity;Neurons;Neurosciences;Outcome Measure;Output;Parvalbumins;Patients;Pattern;Performance;Play;Postdoctoral Fellow;pre-clinical;pre-clinical research;Process;programs;Property;Qualitative Methods;Recovery;Recovery of Function;rehabilitation paradigm;rehabilitation strategy;Rehabilitation therapy;Research;Research Personnel;Resolution;response;Role;Secure;Sensory;sensory integration;Shapes;Spinal;Spinal Cord;Spinal cord injury;Spinal cord injury patients;Spinal cord posterior horn;Spinal Cord transection injury;Statistical Data Interpretation;Synapses;System;Techniques;Technology;Testing;Therapeutic Intervention;Three-Dimensional Imaging;tool;Touch sensation;Training;Training Programs;translational barrier;treadmill;treadmill training;Visualization;Walking;Work

PROJECT_TITLE: Bringing the clinic to the lab: the effects of forced and non-forced rehabilitation on functional recovery after spinal cord injury

STUDY_SECTION: NST

STUDY_SECTION_NAME: NST-2 Study Section [NST-2]


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

PHR: Project Narrative The proposed research on the role of cellular surfaces in controlling biomolecular condensation is relevant to public health because condensates are involved in the formation of pathological aggregates that cause neurodegenerative diseases like amyotrophic lateral sclerosis. Therefore, the proposed research is relevant to the part of NIH’s mission that seeks to develop fundamental knowledge that will help to reduce the burdens of human disability and disease. Ultimately, it is envisioned that an enhanced, mechanistic understanding of how cells regulate biomolecular condensation will enable its clinical manipulation, providing new approaches for treating diseases that arise from disruptions to this fundamental cellular process.

PI_NAMEs: SNEAD, WILTON THOMAS (contact)

PROGRAM_OFFICER_NAME: STOKES, KALYNDA K

PROJECT_TERMS: Acceleration;Amyotrophic Lateral Sclerosis;Architecture;Award;Binding Proteins;Biochemistry;Biological;Biological Models;Biological Process;Biology;career;cell assembly;Cell Cycle;Cell Nucleus;Cell Physiology;Cells;Clinical;clinical development;Collaborations;Communities;Creativeness;Cytoplasm;disability;Discipline;Disease;DNA;driving force;Educational workshop;Endoplasmic Reticulum;Environment;experience;flexibility;Fostering;Foundations;Freedom;Heterogeneity;Human;innovation;interest;Intervention;Knowledge;Learning;Length;Lipid Bilayers;Liquid substance;Maps;mathematical model;Measures;Membrane;Membrane Lipids;Mentors;Messenger RNA;meter;Mission;Molecular;Molecular Conformation;Morphology;mRNA Translation;Neurodegenerative Disorders;novel strategies;Nuclear;Nuclear Matrix;Nucleic Acids;Outcome;Pathologic;Physical condensation;physical property;Polymers;Post-Transcriptional Regulation;Process;Property;Proteins;Public Health;Quantitative Microscopy;Radial;reconstitution;recruit;Regulation;Research;RNA;RNA Conformation;RNA Probes;RNA-Binding Protein FUS;Role;Sampling;Scientist;self assembly;skills;Sorting;Specific qualifier value;Structure;Surface;symposium;Training;Translations;two-dimensional;United States National Institutes of Health;Universities;Untranslated RNA;Work

PROJECT_TITLE: Cellular surfaces as regulators of biomolecular condensate assembly