grant

Circadian and mitochondrial dysfunction in alcohol-related liver disease

Organization UNIVERSITY OF ALABAMA AT BIRMINGHAMLocation BIRMINGHAM, UNITED STATESPosted 10 May 2023Deadline 31 Mar 2028
NIHUS FederalResearch GrantFY2025ARNTLARNTL geneAccelerationActive OxygenAffectAlcohol Chemical ClassAlcohol DrinkingAlcohol HepatotoxicityAlcohol consumptionAlcohol-Induced DisordersAlcoholic HepatotoxicityAlcoholic Liver DiseasesAlcoholsAreaAutomobile DrivingBMAL1BioenergeticsBiologic OscillatorBiologic PacemakersBiologicalBiological OscillatorsBiological PacemakersBlood SerumCause of DeathChronicChronobiologyCircadian DysregulationCircadian RhythmsClinicalComplexConsumptionCyclicityCytochrome OxidaseDNA mutationDataDietDiseaseDisorderDiurnal RhythmDoxycyclineDysfunctionE4BP4Electron Transport Complex IVEndogenous OscillatorsEnvironmental FactorEnvironmental Risk FactorEnzyme GeneEnzymesEtOH drinkingEtOH useExhibitsFerrocytochrome c Oxygen OxidoreductaseFunctional disorderGene TranscriptionGenerationsGenesGeneticGenetic ChangeGenetic TranscriptionGenetic defectGenetic mutationGenotypeGoalsH2O2HealthHepaticHepatic CellsHepatic DisorderHepatic Parenchymal CellHepatic mitochondriaHepatocyteHistopathologyHydrogen PeroxideHydroperoxideImpairmentInjuryInjury to LiverKnock-outKnockoutKnowledgeLiverLiver CellsLiver MitochondriaLiver diseasesMaintenanceMeasuresMetabolic dysfunctionMethodsMiceMice MammalsMitochondriaMitochondrial DNAModelingMolecularMurineMusMutationNyctohemeral RhythmOrganOutcomes ResearchOutputOxidation-ReductionOxygen RadicalsPathogenesisPathologicPathologyPatientsPeriodicityPhysiologicPhysiologicalPhysiopathologyPlayPro-OxidantsProteomeProteomicsR-Series Research ProjectsR01 MechanismR01 ProgramRNA ExpressionReactive Oxygen SpeciesRedoxResearch GrantsResearch Project GrantsResearch ProjectsResolutionRespirationRhythmicityRoleSerumSiteSpirometryStimulusStressSystemTestingTetTetanus Helper PeptideTherapeuticTranscriptionTriacylglycerolTriglyceridesTwenty-Four Hour RhythmUnited StatesVariantVariationVibramycinalcohol induced hepatic injuryalcohol induced injuryalcohol induced liver disorderalcohol induced liver injuryalcohol ingestionalcohol intakealcohol product usealcohol related liver diseasealcohol usealcohol use preventionalcohol-associated liver diseasealcohol-induced damagealcohol-induced hepatic dysfunctionalcohol-induced liver diseasealcohol-induced liver dysfunctionalcohol-mediated liver dysfunctionalcohol-mediated liver injuryalcohol-related liver diseasealcoholic beverage consumptionalcoholic drink intakealcoholic liver injuryalpha-6-Deoxyoxytetracyclinearyl hydrocarbon receptor nuclear translocator-likebiologicchronic EtOH drinkingchronic alcohol consumptionchronic alcohol drinkingchronic alcohol ingestionchronic alcohol usechronic ethanol consumptionchronic ethanol drinkingchronic ethanol ingestioncircadiancircadian abnormalitycircadian clockcircadian disruptioncircadian disturbancecircadian dysfunctioncircadian impairmentcircadian pacemakercircadian processcircadian rhythmicitycompare to controlcomparison controlcomplex IVcytochrome c oxidasedaily biorhythmdeter alcohol usedietsdiurnal variationdrivingdrug developmentdrug discoveryeffective therapyeffective treatmentenvironmental riskenzyme activityethanol consumptionethanol drinkingethanol induced hepatic injuryethanol induced injuryethanol induced liver disorderethanol induced liver injuryethanol ingestionethanol intakeethanol liver diseaseethanol product useethanol useethanol-induced disorderethanol-induced hepatic dysfunctionethanol-induced liver diseaseethanol-induced liver dysfunctionethanol-mediated liver dysfunctionethanol-mediated liver injuryextracellularfatty acid oxidationgenome mutationglucose metabolismglycogen metabolismhepatic body systemhepatic damagehepatic diseasehepatic injuryhepatic organ systemhepatopathyimprovedinjuriesinsightlipidomeliver damageliver disorderliver injurymitochondrialmitochondrial dysfunctionmitochondrial metabolismmouse modelmtDNAmurine modelnew approachesnew drug treatmentsnew drugsnew pharmacological therapeuticnew therapeuticsnew therapynext generation therapeuticsnicotinamide ribonucleosidenicotinamide ribosenicotinamide ribosidenicotinamide-beta-ribosidenovel approachesnovel drug treatmentsnovel drugsnovel pharmaco-therapeuticnovel pharmacological therapeuticnovel strategiesnovel strategynovel therapeuticsnovel therapyoxidation reduction reactionpathophysiologypharmacologicpre-clinicalpreclinicalpreventprevent alcohol usepreventable deathpreventable mortalitypreventingresolutionsrespiratoryrespiratory mechanismsmall moleculesocial roletissue repairtranslational impact
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PROJECT SUMMARY
Alcohol-related liver disease (ALD) is the number one cause of death from long-term and excessive alcohol use

in the United States. One early and primary target of alcohol hepatotoxicity is the mitochondrion. Chronic alcohol

consumption severely compromises liver mitochondrial bioenergetic function; however, the specific molecular…

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