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Determining hepatocyte-specific mechanisms by which Ube4A regulates NAFLD/NASH
Organization SAINT LOUIS UNIVERSITYLocation SAINT LOUIS, UNITED STATESPosted 15 Mar 2023Deadline 9 Mar 2025 ⚠️
NIHUS FederalResearch GrantFY20252-Methyl-1,4-naphthalenedione2-Methyl-1,4-naphthoquinone2-MethylnaphthoquinoneAPF-1ATP-Dependent Proteolysis Factor 1Adeno-Associated VirusesAdipocytesAdipose CellAssayAutoregulationBioassayBiological AssayBody TissuesCancersCaspaseCaspase GeneCell BodyCell DeathCell Death InductionCell SurvivalCell ViabilityCell-Death ProteaseCellsCellular Metabolic ProcessCellular StressCellular Stress ResponseCessation of lifeChiro-InositolCirrhosisCysteine EndopeptidasesCysteine ProteaseCysteine ProteinasesDNA DamageDNA InjuryDeathDependoparvovirusDependovirusDevelopmentDiphosphatesDiseaseDisorderDrug TherapyE3 LigaseE3 Ubiquitin LigaseER stressEconomicsEndoplasmic ReticulumEnergy ExpenditureEnergy MetabolismEnzyme GeneEnzymesErgastoplasmFat CellsFatty AcidsFatty LiverGenomeGlycolysisGoalsHMG-20Hepatic CellsHepatic Parenchymal CellHepatocyteHexadecanoatesHigh Mobility Protein 20HomeostasisHumanHyperinsulinemiaHyperinsulinismICE-like proteaseImpairmentIn VitroInflammationInjuryInjury to LiverInositolInsulin ResistanceIntermediary MetabolismKO miceKnock-outKnock-out MiceKnockoutKnockout MiceLinkLipocytesLiverLiver CellsLiver SteatosisMalignant NeoplasmsMalignant TumorMature LipocyteMature fat cellMediatingMediatorMenadioneMesoinositolMetabolicMetabolic ProcessesMetabolic Protein DegradationMetabolic dysfunctionMetabolismMiceMice MammalsModelingModern ManMurineMusMutateNAFLDNASHNuclearNull MouseObese MiceObesityOxidative StressOxidative Stress InductionOxygen ConsumptionPalmitatesPathway interactionsPatientsPharmacological TreatmentPharmacotherapyPhysiological HomeostasisProcessProductionProtein TurnoverProteinsProteomePublic HealthPyrophosphatesRNA SeqRNA sequencingRNAseqRegulationRegulatory Protein DegradationResearchRisk FactorsRoleSiteStressSystemTestingTherapeuticTissuesTunicamycinUbiquitilationUbiquitinUbiquitin Protein LigaseUbiquitin-Protein Ligase ComplexesUbiquitin-Protein Ligase E3UbiquitinationUbiquitinoylationVitamin K 3Vitamin K3adeno associated virus groupadenoviral mediatedadenovirus-mediatedadipositycell metabolismcell stresscellular metabaolismcirrhoticcorpulencecystein proteasecystein proteinasecysteine endopeptidasedevelopmentaldiet-associated obesitydiet-induced obesitydiet-related obesitydrug interventiondrug treatmenteconomicendoplasmic reticulum stressglucose uptakehepatic body systemhepatic damagehepatic injuryhepatic organ systemhepatic steatosishepatosteatosisin vivoinhibitorinjuriesinnovateinnovationinnovativeinsulin resistantinsulin sensitivityinsulin signalinginsulin toleranceliver damageliver injurymalignancymutantnecrocytosisneoplasm/cancernew drug treatmentsnew drugsnew pharmacological therapeuticnew therapeutic approachnew therapeutic interventionnew therapeutic strategiesnew therapeuticsnew therapynew therapy approachesnew treatment approachnew treatment strategynext generation therapeuticsnon-alcohol fatty liver diseasenon-alcohol induced steatohepatitisnon-alcoholic fatty liver diseasenon-alcoholic liver diseasenon-alcoholic steato-hepatitisnon-alcoholic steatohepatitisnonalcoholic fatty liver diseasenonalcoholic steato-hepatitisnonalcoholic steatohepatitisnovelnovel drug treatmentsnovel drugsnovel pharmaco-therapeuticnovel pharmacological therapeuticnovel therapeutic approachnovel therapeutic interventionnovel therapeutic strategiesnovel therapeuticsnovel therapynovel therapy approachob/ob mouseobese individualsobese peopleobese personobese populationobese subjectsobesigenicobesogenicoverexpressoverexpressionpathwaypharmaceutical interventionpharmacologicpharmacological interventionpharmacological therapypharmacology interventionpharmacology treatmentpharmacotherapeuticspreventpreventingprotein degradationprotein homeostasisproteostasisresponsesocialsocial rolestressortooltranscriptome sequencingtranscriptomic sequencingubiquinationubiquitin conjugationubiquitin-protein ligaseuptakewestern dietwestern-style dietwestern-type diet
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Description preview
Project summary
Obesity is a major risk factor for NAFLD/NASH. In obesity, energy accumulation causes metabolic dysfunction
and endoplasmic reticulum (ER) and oxidative stress, leading to tissue inflammation and injury, which are
hallmarks of NASH. The DNA damage response and unfolded protein response are vital to maintain the integrity
of…
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