2024
CYP2E1 in 1,4-dioxane metabolism and liver toxicity: insights from CYP2E1 knockout mice study
Wang Y, Charkoftaki G, Orlicky D, Davidson E, Aalizadeh R, Sun N, Ginsberg G, Thompson D, Vasiliou V, Chen Y. CYP2E1 in 1,4-dioxane metabolism and liver toxicity: insights from CYP2E1 knockout mice study. Archives Of Toxicology 2024, 98: 3241-3257. PMID: 39192018, DOI: 10.1007/s00204-024-03811-5.Peer-Reviewed Original ResearchCYP2E1-null miceLiver toxicityDrinking waterOxidative DNA damageLiver carcinogenAbstract1,4-DioxaneDNA damage repair responseImpaired DNA damage repairWater contaminationOxidative stressElevated oxidative stressEnvironmental pollutionKnockout mouse studiesDamage repair responseCYP2E1-nullMale wildtypeWT miceDNA damageDX exposureRisk assessmentRedox dysregulationCYP2E1 inductionLiver oxidative stressHigh dosesMouse studiesGlutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression
Asantewaa G, Tuttle E, Ward N, Kang Y, Kim Y, Kavanagh M, Girnius N, Chen Y, Rodriguez K, Hecht F, Zocchi M, Smorodintsev-Schiller L, Scales T, Taylor K, Alimohammadi F, Duncan R, Sechrist Z, Agostini-Vulaj D, Schafer X, Chang H, Smith Z, O’Connor T, Whelan S, Selfors L, Crowdis J, Gray G, Bronson R, Brenner D, Rufini A, Dirksen R, Hezel A, Huber A, Munger J, Cravatt B, Vasiliou V, Cole C, DeNicola G, Harris I. Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression. Nature Communications 2024, 15: 6152. PMID: 39034312, PMCID: PMC11271484, DOI: 10.1038/s41467-024-50454-2.Peer-Reviewed Original ResearchConceptsGlutamate-cysteine ligase catalytic subunitLipid abundanceLipogenic enzyme expressionAbundance in vivoLipid productionCatalytic subunitRepress Nrf2Transcription factorsNrf2 repressionAdult tissuesSynthesis of GSHEnzyme expressionNon-redundantRedox bufferMouse liverLoss of GSHTriglyceride productionIn vivo modelsAbundanceGlutathione synthesisLiver balanceFat storesOxidative stressLipidDeletionA Th17 cell-intrinsic glutathione/mitochondrial-IL-22 axis protects against intestinal inflammation
Bonetti L, Horkova V, Grusdat M, Longworth J, Guerra L, Kurniawan H, Franchina D, Soriano-Baguet L, Binsfeld C, Verschueren C, Spath S, Ewen A, Koncina E, Gérardy J, Kobayashi T, Dostert C, Farinelle S, Härm J, Fan Y, Chen Y, Harris I, Lang P, Vasiliou V, Waisman A, Letellier E, Becher B, Mittelbronn M, Brenner D. A Th17 cell-intrinsic glutathione/mitochondrial-IL-22 axis protects against intestinal inflammation. Cell Metabolism 2024, 36: 1726-1744.e10. PMID: 38986617, DOI: 10.1016/j.cmet.2024.06.010.Peer-Reviewed Original ResearchReactive oxygen speciesMitochondrial functionCatalytic subunit of glutamate cysteine ligaseMitochondrial gene expressionDecreased cellular ATPPhosphorylation of 4E-BP1Disrupt mitochondrial functionReduced phosphorylation of 4E-BP1T cell-specific ablationCell's antioxidant mechanismsCell-specific ablationCatalytic subunitIL-22Cellular signalingIntestinal homeostasisIL-22 productionSignificant reactive oxygen speciesSubunit of glutamate cysteine ligaseGene expressionReduced IL-22 productionReduced phosphorylationCellular ATPGut protectionProtein synthesisGlutamate cysteine ligaseRetinol-binding protein 4 as a promising serum biomarker for the diagnosis and prognosis of hepatocellular Carcinoma.
Wan F, Zhu Y, Wu F, Huang X, Chen Y, Zhou Y, Li H, Liang L, Qin L, Wang Q, He M. Retinol-binding protein 4 as a promising serum biomarker for the diagnosis and prognosis of hepatocellular Carcinoma. Transl Oncol 2024, 45: 101979. PMID: 38728873, DOI: 10.1016/j.tranon.2024.101979.Peer-Reviewed Original ResearchLiver epigenomic signature associated with chronic oxidative stress in a mouse model of glutathione deficiency
Hong S, Yu X, Zhu Y, Chen Y. Liver epigenomic signature associated with chronic oxidative stress in a mouse model of glutathione deficiency. Chemico-Biological Interactions 2024, 398: 111093. PMID: 38830566, PMCID: PMC11223951, DOI: 10.1016/j.cbi.2024.111093.Peer-Reviewed Original ResearchS-adenosyl methionineGene promoterArray-based DNA methylation profilingPeripheral blood cellsFatty liver diseaseDNA methylation profilesDNA methylation statusMethyl donor S-adenosyl methionineGene promoter regionFunctional enrichment analysisMethylation enrichmentMouse modelOxidative stressLiver epigenomeEpigenomic changesIn vivo interplayMethylation profilesPromoter regionEpigenetic regulationEpigenomic signaturesEpigenetic mechanismsLipid homeostasisBlood cellsEnrichment analysisCellular survival1,4-Dioxane
Stouffer A, Erickson C, Krick M, Chen Y, Ginsberg G, Loch-Caruso R, Jones R, Madrigal J, Thompson D, Vasliou V. 1,4-Dioxane. 2024, 843-849. DOI: 10.1016/b978-0-12-824315-2.00831-9.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsPersistent environmental contaminationEnvironmental contaminationEnvironmental behaviorEnvironmental releaseChemical intermediatesWater solubilityPotential negative health effectsDioxaneRecent decadesSoilConsumer productsGroundwaterContaminationHealth effectsSolventSolubilityIntermediatesNegative health effectsStabilizerManagementUsesProductsUseToxicityExposure
2023
Multi-omics profiling reveals cellular pathways and functions regulated by ALDH1B1 in colon cancer cells
Wang Y, Popovic Z, Charkoftaki G, Garcia-Milian R, Lam T, Thompson D, Chen Y, Vasiliou V. Multi-omics profiling reveals cellular pathways and functions regulated by ALDH1B1 in colon cancer cells. Chemico-Biological Interactions 2023, 384: 110714. PMID: 37716420, PMCID: PMC10807983, DOI: 10.1016/j.cbi.2023.110714.Peer-Reviewed Original ResearchColon cancer cellsCellular stress response pathwaysStress response pathwaysMulti-omics analysisCancer cellsSecond messenger signalingMulti-omics profilingNew molecular informationFunctional annotationCellular functionsResponse pathwaysKinase signalingCellular pathwaysColon adenocarcinoma cell lineHuman colon adenocarcinoma cell lineApoptosis signalingEnrichment analysisAldehyde dehydrogenase 1B1Molecular signaturesAdenocarcinoma cell lineMolecular informationSignalingNovel targetProtein expressionCell linesAn AI-powered patient triage platform for future viral outbreaks using COVID-19 as a disease model
Charkoftaki G, Aalizadeh R, Santos-Neto A, Tan W, Davidson E, Nikolopoulou V, Wang Y, Thompson B, Furnary T, Chen Y, Wunder E, Coppi A, Schulz W, Iwasaki A, Pierce R, Cruz C, Desir G, Kaminski N, Farhadian S, Veselkov K, Datta R, Campbell M, Thomaidis N, Ko A, Thompson D, Vasiliou V. An AI-powered patient triage platform for future viral outbreaks using COVID-19 as a disease model. Human Genomics 2023, 17: 80. PMID: 37641126, PMCID: PMC10463861, DOI: 10.1186/s40246-023-00521-4.Peer-Reviewed Original ResearchConceptsCOVID-19 patientsDisease severityViral outbreaksFuture viral outbreaksLength of hospitalizationIntensive care unitWorse disease prognosisLife-threatening illnessEffective medical interventionsCOVID-19Clinical decision treeGlucuronic acid metabolitesNew potential biomarkersHospitalization lengthCare unitComorbidity dataSerotonin levelsDisease progressionHealthy controlsPatient outcomesDisease prognosisPatient transferPatientsHealthcare resourcesPotential biomarkersFatal Epileptic Seizures in Mice Having Compromised Glutathione and Ascorbic Acid Biosynthesis
Chen Y, Holland K, Shertzer H, Nebert D, Dalton T. Fatal Epileptic Seizures in Mice Having Compromised Glutathione and Ascorbic Acid Biosynthesis. Antioxidants 2023, 12: 448. PMID: 36830006, PMCID: PMC9952205, DOI: 10.3390/antiox12020448.Peer-Reviewed Original ResearchDKO miceEpileptic seizuresKnockout miceAA supplementationAdult DKO miceFatal epileptic seizuresSpontaneous epileptic seizuresDietary ascorbic acidTissue GSH levelsDouble knockout miceNormal brain functionFunctional crosstalkNeuronal lossHippocampal pathologyGlutamatergic neurotransmissionGlial proliferationBrain damageNeuronal healthPostnatal dayBrain pathologyRate-limiting enzymeSeizuresBrain functionMiceGSH levels
2022
Mechanistic considerations in 1,4-dioxane cancer risk assessment
Ginsberg G, Chen Y, Vasiliou V. Mechanistic considerations in 1,4-dioxane cancer risk assessment. Current Opinion In Environmental Science & Health 2022, 30: 100407. PMID: 37091947, PMCID: PMC10120849, DOI: 10.1016/j.coesh.2022.100407.Peer-Reviewed Original ResearchCarcinogenic effectsLinear low-dose extrapolationGenders of ratsDose responseInduction of CYP2E1Human liver cancerCancer risk assessmentLow-dose extrapolationLiver cancerLow doseAnimal studiesDose levelsChronic exposureLow human exposureDose extrapolationCarcinogenic responseStandard test batteryVivo genotoxicityRisk assessmentOxidative stressDisease-related processesOwn metabolismLess likelihoodMode of actionHuman exposureProteomic profiling reveals an association between ALDH and oxidative phosphorylation and DNA damage repair pathways in human colon adenocarcinoma stem cells
Wang Y, Chen Y, Garcia-Milian R, Golla JP, Charkoftaki G, Lam TT, Thompson DC, Vasiliou V. Proteomic profiling reveals an association between ALDH and oxidative phosphorylation and DNA damage repair pathways in human colon adenocarcinoma stem cells. Chemico-Biological Interactions 2022, 368: 110175. PMID: 36162455, PMCID: PMC9891852, DOI: 10.1016/j.cbi.2022.110175.Peer-Reviewed Original ResearchConceptsCancer stem cellsProteomic profilingOxidative phosphorylationLabel-free quantitative proteomic analysisDNA damage repair pathwaysQuantitative proteomic analysisAldehyde dehydrogenase familyColon cancer stem cellsCOLO320DM cellsStem cellsNucleotide excision repairDamage repair pathwaysIngenuity Pathway AnalysisCell populationsProteomic analysisProteomic datasetsDehydrogenase familyMetabolic switchProteomic studiesRepair pathwaysCellular pathwaysALDH enzymatic activityCellular survivalExcision repairALDH activityExposure to Per- and polyfluoroalkyl substances is associated with altered pancreatic β-cell function
Goodrich J, Davidson* E, Baumert B, Chen Y, Walker D, Lin X, Hu X, Alderete T, Chen Z, Valvi D, Fuentes Z, Rock S, Berhane K, Gilliland F, Jones D, Goran M, Conti D, Vasiliou† V, Chatzi† L. Exposure to Per- and polyfluoroalkyl substances is associated with altered pancreatic β-cell function. ISEE Conference Abstracts 2022, 2022 DOI: 10.1289/isee.2022.p-0352.Peer-Reviewed Original ResearchOxidative stress, glutathione, and CYP2E1 in 1,4-dioxane liver cytotoxicity and genotoxicity: insights from animal models
Wang Y, Charkoftaki G, Davidson E, Orlicky D, Tanguay R, Thompson D, Vasiliou V, Chen Y. Oxidative stress, glutathione, and CYP2E1 in 1,4-dioxane liver cytotoxicity and genotoxicity: insights from animal models. Current Opinion In Environmental Science & Health 2022, 29: 100389. PMID: 37483863, PMCID: PMC10361651, DOI: 10.1016/j.coesh.2022.100389.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsOxidative stressUnique mouse modelRelevant low dosesDirect genotoxic effectsLiver cytotoxicityCYP2E1 activationMouse modelAnimal modelsHuman studiesCarcinogenic pathwaysLiver carcinogenicityLow dosesCausal roleGenotoxic effectsHuman exposureUndetermined mechanismPublic healthCarcinogenicityLiver genotoxicityDrinking water contaminantsMechanistic dataGenotoxicityFuture animalCytotoxicityCYP2E1Glutathione-dependent redox balance characterizes the distinct metabolic properties of follicular and marginal zone B cells
Franchina DG, Kurniawan H, Grusdat M, Binsfeld C, Guerra L, Bonetti L, Soriano-Baguet L, Ewen A, Kobayashi T, Farinelle S, Minafra AR, Vandamme N, Carpentier A, Borgmann FK, Jäger C, Chen Y, Kleinewietfeld M, Vasiliou V, Mittelbronn M, Hiller K, Lang PA, Brenner D. Glutathione-dependent redox balance characterizes the distinct metabolic properties of follicular and marginal zone B cells. Nature Communications 2022, 13: 1789. PMID: 35379825, PMCID: PMC8980022, DOI: 10.1038/s41467-022-29426-x.Peer-Reviewed Original ResearchConceptsElectron transport chainMarginal zone B cellsMitochondrial electron transport chainGlutamate-cysteine ligaseCatalytic subunitRedox controlCell-specific ablationRedox balanceTransport chainMetabolic dependenciesCysteine ligaseProtein synthesisMetabolite succinateMTOR activationGlutathione synthesisATP levelsMetabolic propertiesB cellsMetabolic principlesMetabolic featuresDistinct metabolic propertiesMZBCellsActivationLigaseLipidomics and Redox Lipidomics Indicate Early Stage Alcohol‐Induced Liver Damage
Koelmel JP, Tan WY, Li Y, Bowden JA, Ahmadireskety A, Patt AC, Orlicky DJ, Mathé E, Kroeger NM, Thompson DC, Cochran JA, Golla JP, Kandyliari A, Chen Y, Charkoftaki G, Guingab‐Cagmat J, Tsugawa H, Arora A, Veselkov K, Kato S, Otoki Y, Nakagawa K, Yost RA, Garrett TJ, Vasiliou V. Lipidomics and Redox Lipidomics Indicate Early Stage Alcohol‐Induced Liver Damage. Hepatology Communications 2022, 6: 513-525. PMID: 34811964, PMCID: PMC8870008, DOI: 10.1002/hep4.1825.Peer-Reviewed Original ResearchConceptsAlcoholic fatty liver diseaseEthanol-treated miceFatty liver diseaseAlcohol consumption altersRegulation of triglycerideLiver lipidomeRegulation of phosphatidylcholineHepatic inflammationLiver biopsyLiver diseaseComprehensive time-course studyLiver damageHistological signsEarly biomarkersHistological markersMouse modelTime-course studyLiver tissueTriglyceridesHistological analysisEarly detectionLipid accumulationLiverMajor lipid classesDiet modelOxidative stress induces inflammation of lens cells and triggers immune surveillance of ocular tissues
Thompson B, Davidson EA, Chen Y, Orlicky DJ, Thompson DC, Vasiliou V. Oxidative stress induces inflammation of lens cells and triggers immune surveillance of ocular tissues. Chemico-Biological Interactions 2022, 355: 109804. PMID: 35123994, PMCID: PMC9136680, DOI: 10.1016/j.cbi.2022.109804.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcysteineAnimalsButhionine SulfoximineCell LineChemokine CCL7CytokinesDown-RegulationEpithelial CellsEpithelial-Mesenchymal TransitionEyeGlutamate-Cysteine LigaseImmunity, InnateLens, CrystallineLeukocytesMiceMice, Inbred C57BLMice, KnockoutOxidative StressReactive Oxygen SpeciesUp-RegulationConceptsPosterior capsule opacificationCytokine expressionKO miceImmune surveillanceOxidative stressLens epithelial cellsOcular structuresLens cellsDevelopment of PCOEpithelial cellsInnate immune cellsExpression of cytokinesEx vivo inductionOcular surface tissuesExpression of markersImmune response genesCON miceControl miceCapsule opacificationImmune cellsPostnatal dayΑ-SMAMouse modelOcular tissuesVivo induction
2021
Oxidative stress and genotoxicity in 1,4-dioxane liver toxicity as evidenced in a mouse model of glutathione deficiency
Chen Y, Wang Y, Charkoftaki G, Orlicky DJ, Davidson E, Wan F, Ginsberg G, Thompson DC, Vasiliou V. Oxidative stress and genotoxicity in 1,4-dioxane liver toxicity as evidenced in a mouse model of glutathione deficiency. The Science Of The Total Environment 2021, 806: 150703. PMID: 34600989, PMCID: PMC8633123, DOI: 10.1016/j.scitotenv.2021.150703.Peer-Reviewed Original ResearchConceptsOxidative stressLiver cytotoxicityGlutamate-cysteine ligase modifier subunitWild-type micePrimary target organRecent mouse studiesCYP2E1 inductionLiver toxicitySubchronic exposureNrf2 inductionOxidative DNA damageCancer riskMouse modelAnti-oxidative responseDNA damageTarget organsAnimal studiesLiver carcinogenicityRedox dysregulationEarly changesHealth CanadaNull miceMouse studiesNuclear factorCarcinogenic mechanismsImpaired GSH biosynthesis disrupts eye development, lens morphogenesis and PAX6 function
Thompson B, Chen Y, Davidson EA, Garcia-Milian R, Golla JP, Apostolopoulos N, Orlicky DJ, Schey K, Thompson DC, Vasiliou V. Impaired GSH biosynthesis disrupts eye development, lens morphogenesis and PAX6 function. The Ocular Surface 2021, 22: 190-203. PMID: 34425299, PMCID: PMC8560581, DOI: 10.1016/j.jtos.2021.08.010.Peer-Reviewed Original ResearchConceptsHEK293T cellsEye developmentGSH biosynthesisTransactivation activityPax6 functionReactive oxygen speciesSubsequent gene ontologyCell identity genesButhionine sulfoximineEpithelial cell identityRNA-seq analysisIngenuity Pathway AnalysisKey upstream regulatorIdentity genesCell identityGene OntologyRNA-seqImmune response genesBioinformatics analysisResponse genesGlutathione biosynthesisLens morphogenesisMolecular consequencesUpstream regulatorMicrophthalmia phenotypeIdentification of Dose-Dependent DNA Damage and Repair Responses From Subchronic Exposure to 1,4-Dioxane in Mice Using a Systems Analysis Approach
Charkoftaki G, Golla JP, Santos-Neto A, Orlicky DJ, Garcia-Milian R, Chen Y, Rattray NJW, Cai Y, Wang Y, Shearn CT, Mironova V, Wang Y, Johnson CH, Thompson DC, Vasiliou V. Identification of Dose-Dependent DNA Damage and Repair Responses From Subchronic Exposure to 1,4-Dioxane in Mice Using a Systems Analysis Approach. Toxicological Sciences 2021, 183: 338-351. PMID: 33693819, PMCID: PMC8921626, DOI: 10.1093/toxsci/kfab030.Peer-Reviewed Original ResearchConceptsDX exposureBile acid quantificationRepair responseBDF-1 miceDNA damageDose-dependent DNA damageEffects of exposureHistopathological studySubchronic exposureImmunohistochemical analysisLiver carcinogenLiver carcinogenicityLiver transcriptomicsDrinking waterMetabolomic profilingMicePotential mechanismsLiverEnvironmental chemicalsState maximum contaminant levelToxic effectsCell deathExposureOxidative stress responsePresent study
2020
Interplay between APC and ALDH1B1 in a newly developed mouse model of colorectal cancer
Golla JP, Kandyliari A, Tan WY, Chen Y, Orlicky DJ, Thompson DC, Shah YM, Vasiliou V. Interplay between APC and ALDH1B1 in a newly developed mouse model of colorectal cancer. Chemico-Biological Interactions 2020, 331: 109274. PMID: 33007288, PMCID: PMC9201852, DOI: 10.1016/j.cbi.2020.109274.Peer-Reviewed Original ResearchConceptsColorectal cancerColonic adenomasPresent preliminary studyMouse modelConsecutive daysLarge colonic adenomaPresence of adenomasApc mouse modelColon tumor growthMouse xenograft modelColon epithelial cellsFurther mechanistic studiesCancer mortalityKO miceLeading causeColorectal adenomasCRC developmentImmunohistochemical analysisXenograft modelTumor growthColorectal tumorigenesisAdenomasExpression scoreMale ApcMice