2022
Use of clinical chemistry health outcomes and PFAS chain length to predict 28-day rodent oral toxicity
Bellia G, Bilott R, Sun N, Thompson D, Vasiliou V. Use of clinical chemistry health outcomes and PFAS chain length to predict 28-day rodent oral toxicity. Toxicology Mechanisms And Methods 2022, 33: 378-387. PMID: 36446747, PMCID: PMC10625160, DOI: 10.1080/15376516.2022.2150591.Peer-Reviewed Original ResearchLiver metabolomics identifies bile acid profile changes at early stages of alcoholic liver disease in mice
Charkoftaki G, Tan WY, Berrios-Carcamo P, Orlicky DJ, Golla JP, Garcia-Milian R, Aalizadeh R, Thomaidis NS, Thompson DC, Vasiliou V. Liver metabolomics identifies bile acid profile changes at early stages of alcoholic liver disease in mice. Chemico-Biological Interactions 2022, 360: 109931. PMID: 35429548, PMCID: PMC9364420, DOI: 10.1016/j.cbi.2022.109931.Peer-Reviewed Original ResearchConceptsAlcoholic liver diseaseEthanol-consuming miceAlcohol consumptionLiver diseaseDevelopment of ALDBile acid changesChronic alcohol drinkingChronic alcohol consumptionLieber-DeCarli dietAlcohol-induced alterationsGlobal healthcare problemBile acid biosynthesisAlcohol drinkingLiver histopathologyTissue injuryClinical consequencesUntargeted metabolomics analysisEarly stagesComplex pathologyMinimal changesUntargeted metabolomics approachEarly onsetHealthcare problemMiceLiverOxidative 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
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
2019
Genetics and functions of the retinoic acid pathway, with special emphasis on the eye
Thompson B, Katsanis N, Apostolopoulos N, Thompson DC, Nebert DW, Vasiliou V. Genetics and functions of the retinoic acid pathway, with special emphasis on the eye. Human Genomics 2019, 13: 61. PMID: 31796115, PMCID: PMC6892198, DOI: 10.1186/s40246-019-0248-9.Peer-Reviewed Original ResearchConceptsRequirement of RAEmbryonic developmentRetinoic acidAnterior segment formationRetinoic acid pathwayRas signalingPotent morphogenEye developmentOptic cup formationPostnatal lethalitySegment formationAcid pathwayCup formationNormal developmentOptic vesicleMultistep processParacrine fashionPathwayRecent advancesMorphogensGenesGeneticsMutationsVesiclesLethalityGlutathione deficiency-elicited reprogramming of hepatic metabolism protects against alcohol-induced steatosis
Chen Y, Manna SK, Golla S, Krausz KW, Cai Y, Garcia-Milian R, Chakraborty T, Chakraborty J, Chatterjee R, Thompson DC, Gonzalez FJ, Vasiliou V. Glutathione deficiency-elicited reprogramming of hepatic metabolism protects against alcohol-induced steatosis. Free Radical Biology And Medicine 2019, 143: 127-139. PMID: 31351176, PMCID: PMC6848780, DOI: 10.1016/j.freeradbiomed.2019.07.025.Peer-Reviewed Original ResearchMeSH KeywordsAcetyl Coenzyme AAlcohol DrinkingAMP-Activated Protein KinasesAnimalsEthanolFatty AcidsFatty LiverGlucuronic AcidGlutamate-Cysteine LigaseGlutamatesGlutathioneHomeostasisLipogenesisLiverMaleMiceMice, Inbred C57BLMice, KnockoutOligonucleotide Array Sequence AnalysisOxidation-ReductionOxidative StressPentose Phosphate PathwayProtective AgentsTranscription, GeneticConceptsGlutamate-cysteine ligase modifier subunit geneProtein kinase pathwayAcetyl-CoA fluxMultiple cellular pathwaysAlcohol-induced steatosisCellular stressNucleotide biosynthesisLiver microarray analysisGlobal profilingSubunit geneCellular pathwaysMetabolic reprogrammingKinase pathwayMicroarray analysisMolecular mechanismsGSH poolCellular responsesMetabolic pathwaysLower GSHMolecular pathwaysMetabolic homeostasisAmino acidsDepletion of glutathioneCritical pathogenic eventGlucuronate pathwayExpression, purification and crystallization of the novel Xenopus tropicalis ALDH16B1, a homologue of human ALDH16A1
Pantouris G, Dioletis E, Chen Y, Thompson DC, Vasiliou V, Lolis EJ. Expression, purification and crystallization of the novel Xenopus tropicalis ALDH16B1, a homologue of human ALDH16A1. Chemico-Biological Interactions 2019, 304: 168-172. PMID: 30894314, PMCID: PMC6746316, DOI: 10.1016/j.cbi.2019.03.009.Peer-Reviewed Original ResearchConceptsAldehyde dehydrogenaseCritical Cys residuesPreliminary crystallographic analysisGenomic analysisSf9 cellsCys residuesALDH16A1Novel familyLower animalsSize exclusion chromatographyActive siteStructure determinationMetabolomics studiesCrystallographic analysisCellsMammalsHomologuesGenesExclusion chromatographyFishStructural characteristicsFrogsPathogenesis of goutUnique structural characteristicsResiduesHepatic metabolic adaptation in a murine model of glutathione deficiency
Chen Y, Golla S, Garcia-Milian R, Thompson DC, Gonzalez FJ, Vasiliou V. Hepatic metabolic adaptation in a murine model of glutathione deficiency. Chemico-Biological Interactions 2019, 303: 1-6. PMID: 30794799, PMCID: PMC6743730, DOI: 10.1016/j.cbi.2019.02.015.Peer-Reviewed Original ResearchConceptsCellular non-protein thiolsMetabolic adaptationGlutamate-cysteine ligase modifier subunitNon-protein thiolsHepatic metabolic adaptationCellular redoxGlobal profilingGSH homeostasisModifier subunitLiver developmentBiochemical mechanismsMetabolic homeostasisAmino acidsGclm null miceDefense mechanismsEnvironmental insultsOxidative damageFatty liver developmentNull miceSpectrum of changesNucleic acidsMetabolic signaturesPivotal roleHomeostasisGlutathione deficiencyUpdate on the human and mouse lipocalin (LCN) gene family, including evidence the mouse Mup cluster is result of an “evolutionary bloom”
Charkoftaki G, Wang Y, McAndrews M, Bruford EA, Thompson DC, Vasiliou V, Nebert DW. Update on the human and mouse lipocalin (LCN) gene family, including evidence the mouse Mup cluster is result of an “evolutionary bloom”. Human Genomics 2019, 13: 11. PMID: 30782214, PMCID: PMC6381713, DOI: 10.1186/s40246-019-0191-9.Peer-Reviewed Original ResearchConceptsMajor urinary protein genesKingdoms of lifeLipocalin gene familyGene familyMUP genesMouse genomeHuman genomeProtein geneChromosome 4Regulation of glucoseBarrel structurePhysiological processesΒ-strandsPhysiological functionsSecretory tissueGenesScent marksPseudogenesGenomeLipid metabolismBloomsEvidence pointsSyntenicImportant roleSteroid hormones
2018
Engineered Animal Models Designed for Investigating Ethanol Metabolism, Toxicity and Cancer
Marshall S, Chen Y, Singh S, Berrios-Carcamo P, Heit C, Apostolopoulos N, Golla JP, Thompson DC, Vasiliou V. Engineered Animal Models Designed for Investigating Ethanol Metabolism, Toxicity and Cancer. Advances In Experimental Medicine And Biology 2018, 1032: 203-221. PMID: 30362100, PMCID: PMC6743736, DOI: 10.1007/978-3-319-98788-0_14.ChaptersConceptsExact molecular mechanismsMouse modelCellular proteinsEthanol-induced tissue injuryEthanol metabolismEngineered Animal ModelsMolecular mechanismsAldehyde dehydrogenasesLong-term alcohol abuseAlcohol-induced diseasesFurther tissue damageAntioxidant glutathioneImportant mouse modelsCurrent understandingLeading causeTissue injuryIntracellular generationAlcohol abuseAlcohol consumptionAnimal modelsPathogenic eventsPathophysiological consequencesTissue damageMetabolismDNA adducts
2017
Nitrogen mustard-induced corneal injury involves the sphingomyelin-ceramide pathway
Charkoftaki G, Jester JV, Thompson DC, Vasiliou V. Nitrogen mustard-induced corneal injury involves the sphingomyelin-ceramide pathway. The Ocular Surface 2017, 16: 154-162. PMID: 29129753, PMCID: PMC7376578, DOI: 10.1016/j.jtos.2017.11.004.Peer-Reviewed Original ResearchConceptsCorneal damageNM exposureSphingomyelin-ceramide pathwayCorneal stromaIrreversible corneal damageNitrogen mustardAltered lipid profileSulfur mustardCorneal injuryLipid profileCentral corneaCorneal epitheliumRabbit eyesSpecific sphingomyelinsPotent vesicantCorneaOrgan cultureStromaLipidomic analysisExposureMorphological changesDamaging effectsDamageInjuryPathwayTranscriptomic analysis and plasma metabolomics in Aldh16a1-null mice reveals a potential role of ALDH16A1 in renal function
Charkoftaki G, Chen Y, Han M, Sandoval M, Yu X, Zhao H, Orlicky DJ, Thompson DC, Vasiliou V. Transcriptomic analysis and plasma metabolomics in Aldh16a1-null mice reveals a potential role of ALDH16A1 in renal function. Chemico-Biological Interactions 2017, 276: 15-22. PMID: 28254523, PMCID: PMC5725231, DOI: 10.1016/j.cbi.2017.02.013.Peer-Reviewed Original ResearchMeSH KeywordsAldehyde DehydrogenaseAnimalsDown-RegulationGene Expression ProfilingKidneyLipidsMetabolomicsMiceMice, Inbred C57BLMice, KnockoutMonocarboxylic Acid TransportersMultidrug Resistance-Associated ProteinsMutation, MissenseSequence Analysis, RNASodium-Phosphate Cotransporter Proteins, Type IUp-RegulationConceptsUric acid homeostasisPlasma metabolomicsElevated serum uric acid levelsSerum uric acid levelsDistal convoluted tubule cellsAcid homeostasisUric acid levelsZone 3 hepatocytesConvoluted tubule cellsSingle nucleotide variantsRenal functionKO miceLipid profileKnockout miceMissense single nucleotide variantsTubule cellsRNA-seq analysisKidneyMouse linesAcid levelsMicePotential roleLipid metabolic processMetabolomic analysisCellular lipids
2016
Corneal haze phenotype in Aldh3a1-null mice: In vivo confocal microscopy and tissue imaging mass spectrometry
Chen Y, Jester JV, Anderson DM, Marchitti SA, Schey KL, Thompson DC, Vasiliou V. Corneal haze phenotype in Aldh3a1-null mice: In vivo confocal microscopy and tissue imaging mass spectrometry. Chemico-Biological Interactions 2016, 276: 9-14. PMID: 28038895, DOI: 10.1016/j.cbi.2016.12.017.Peer-Reviewed Original ResearchMeSH KeywordsAldehyde DehydrogenaseAnimalsCorneaCorneal DiseasesCorneal StromaDiazepam Binding InhibitorDisease Models, AnimalDynamic Light ScatteringEpitheliumEpithelium, CornealHistonesLens, CrystallineLipidsMiceMice, Inbred C57BLMice, KnockoutMicroscopy, ConfocalPhenotypeSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationConceptsImaging mass spectrometryCorneal crystallinsNon-catalytic functionsAcyl-CoA binding proteinFirst genetic animal modelCellular transparencyCorneal epithelial homeostasisCorneal hazeEndogenous proteinsKO miceLipid localizationMixed genetic backgroundKnockout miceCorneal phenotypeEpithelial homeostasisProtein profilesWild-type corneasBinding proteinFunctional roleGenetic backgroundLens cataractMass spectrometryConfocal microscopyMolecular changesPhenotypeCatalase deletion promotes prediabetic phenotype in mice
Heit C, Marshall S, Singh S, Yu X, Charkoftaki G, Zhao H, Orlicky DJ, Fritz KS, Thompson DC, Vasiliou V. Catalase deletion promotes prediabetic phenotype in mice. Free Radical Biology And Medicine 2016, 103: 48-56. PMID: 27939935, PMCID: PMC5513671, DOI: 10.1016/j.freeradbiomed.2016.12.011.Peer-Reviewed Original ResearchConceptsCatalase-knockout (KO) micePancreatic morphological changesImpaired glucose toleranceDevelopment of diabetesSerum insulin levelsPre-diabetic phenotypePre-diabetic statusRNA-seq analysisSignal transduction moleculesMuscle lipid depositionSignal transduction mechanismsGlucose toleranceMetabolic syndromeInsulin levelsNormal chowHepatic triglyceridesObese phenotypeLiver morphologyHigh riskPrediabetic phenotypesKnockout miceLipid depositionBody weightTransduction moleculesMetabolic regulationQuantification of Neural Ethanol and Acetaldehyde Using Headspace GC‐MS
Heit C, Eriksson P, Thompson DC, Charkoftaki G, Fritz KS, Vasiliou V. Quantification of Neural Ethanol and Acetaldehyde Using Headspace GC‐MS. Alcohol Clinical And Experimental Research 2016, 40: 1825-1831. PMID: 27501276, PMCID: PMC5008984, DOI: 10.1111/acer.13156.Peer-Reviewed Original ResearchConceptsAlcohol drinking behaviorEtOH metabolitesMurine brain tissueACh levelsAlcohol consumptionACh concentrationBrain tissueLiver tissueAChAlcohol addictionACh formationBrainDrinking behaviorLow micromolar rangeAlcohol researchTissue analysisTissueNanomolar rangeChromatography-mass spectrometry methodQuantitative assayMass spectrometry methodActive agentsMicromolar rangeSensitive gas chromatography-mass spectrometry methodChronic Glutathione Depletion Confers Protection against Alcohol-induced Steatosis: Implication for Redox Activation of AMP-activated Protein Kinase Pathway
Chen Y, Singh S, Matsumoto A, Manna SK, Abdelmegeed MA, Golla S, Murphy RC, Dong H, Song BJ, Gonzalez FJ, Thompson DC, Vasiliou V. Chronic Glutathione Depletion Confers Protection against Alcohol-induced Steatosis: Implication for Redox Activation of AMP-activated Protein Kinase Pathway. Scientific Reports 2016, 6: 29743. PMID: 27403993, PMCID: PMC4940737, DOI: 10.1038/srep29743.Peer-Reviewed Original ResearchConceptsAlcoholic liver diseaseGclm KO miceLiver steatosisKO miceAlcohol-induced liver steatosisFactor 2 (Nrf2) target genesEthanol-containing liquid dietOxidative stressGclm knockout mouseAlcohol-induced steatosisHepatic lipid profilesProtein kinase pathwayNew therapeutic strategiesNormal hepatic levelsLevels of glutathioneFatty acid oxidationKinase pathwayLiver diseaseLipid profileLiquid dietEthanol clearanceHepatic levelsTherapeutic strategiesKnockout miceSteatosisLetter to the editor for “Update of the human and mouse Fanconi anemia genes”
Nebert DW, Dong H, Bruford EA, Thompson DC, Joenje H, Vasiliou V. Letter to the editor for “Update of the human and mouse Fanconi anemia genes”. Human Genomics 2016, 10: 25. PMID: 27377885, PMCID: PMC4932714, DOI: 10.1186/s40246-016-0081-3.Peer-Reviewed Original ResearchHeme oxygenase 1 protects ethanol-administered liver tissue in Aldh2 knockout mice
Matsumoto A, Thompson D, Chen Y, Vasiliou V, Kawamoto T, Ichiba M. Heme oxygenase 1 protects ethanol-administered liver tissue in Aldh2 knockout mice. Alcohol 2016, 52: 49-54. PMID: 27139237, DOI: 10.1016/j.alcohol.2016.02.004.Peer-Reviewed Original ResearchConceptsAldh2 knockout miceStress-related proteinsOxidative stress-related proteinsAlanine transaminaseAnti-oxidative proteinsKnockout miceHealthy individualsHepatic tumor necrosis factor alphaLiver tissueProtective factorsTumor necrosis factor alphaSerum alanine transaminaseRecent epidemiological studiesNecrosis factor alphaWild-type miceHeme oxygenase-1Cytochrome P450 2E1ALDH2 proteinProteinAldehyde dehydrogenase 2 geneHepatic malondialdehydeMechanistic explanationInflammatory cytokinesEthanol administrationMechanistic hypothesesALDH3A1 Plays a Functional Role in Maintenance of Corneal Epithelial Homeostasis
Koppaka V, Chen Y, Mehta G, Orlicky DJ, Thompson DC, Jester JV, Vasiliou V. ALDH3A1 Plays a Functional Role in Maintenance of Corneal Epithelial Homeostasis. PLOS ONE 2016, 11: e0146433. PMID: 26751691, PMCID: PMC4708999, DOI: 10.1371/journal.pone.0146433.Peer-Reviewed Original ResearchConceptsCorneal cell proliferationCorneal epithelial homeostasisCell proliferationALDH3A1 expressionEpithelial homeostasisHuman corneal epithelial cell lineDouble knockout miceAnti-proliferation effectCorneal epithelial cell lineCorneal epithelial proliferationAldehyde dehydrogenase 1A1Epithelial cell lineCorneal differentiation markersInner ocular tissuesInverse associationFunctional roleEpithelial proliferationKnockout miceP53 expressionCorneal epitheliumOcular tissuesMouse corneaCalcium concentrationMRNA levelsEpithelial differentiationAldehyde Dehydrogenase 1B1 as a Modulator of Pancreatic Adenocarcinoma
Singh S, Arcaroli JJ, Orlicky DJ, Chen Y, Messersmith WA, Bagby S, Purkey A, Quackenbush KS, Thompson DC, Vasiliou V. Aldehyde Dehydrogenase 1B1 as a Modulator of Pancreatic Adenocarcinoma. Pancreas 2016, 45: 117-122. PMID: 26566217, PMCID: PMC5175203, DOI: 10.1097/mpa.0000000000000542.Peer-Reviewed Original ResearchMeSH KeywordsAldehyde DehydrogenaseAldehyde Dehydrogenase 1 FamilyAldehyde Dehydrogenase, MitochondrialAnimalsBiomarkers, TumorCarcinoma, Pancreatic DuctalCell Line, TumorCell ProliferationFemaleGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticHumansImmunohistochemistryMice, NudeNeoplasm InvasivenessPancreatic NeoplasmsRNA InterferenceSignal TransductionTissue Array AnalysisTransfectionTumor BurdenUp-RegulationConceptsALDH1B1 expressionPancreatic cancerPancreatic adenocarcinomaTissue microarrayHuman pancreatic cancer cell linesPancreatic cancer cell linesPancreatic cancer patientsPancreatic ductal carcinomaHuman pancreatic cancerAldehyde dehydrogenase 1B1Potential modulatory rolePancreatic cancer cellsNormal human pancreasCell linesCancer cell linesDuctal carcinomaCancer patientsModulatory roleHuman pancreasGlandular cellsTumor cellsProtein expressionCancer cellsGreater expressionAdenocarcinoma