2023
An 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 biomarkers
2022
Proteomic 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 activity
2021
Impaired 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 phenotype
2019
Expression, 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 characteristicsResidues
2018
Glutathione and Transsulfuration in Alcohol-Associated Tissue Injury and Carcinogenesis
Chen Y, Han M, Matsumoto A, Wang Y, Thompson DC, Vasiliou V. Glutathione and Transsulfuration in Alcohol-Associated Tissue Injury and Carcinogenesis. Advances In Experimental Medicine And Biology 2018, 1032: 37-53. PMID: 30362089, PMCID: PMC6743726, DOI: 10.1007/978-3-319-98788-0_3.ChaptersConceptsGSH biosynthesisAbundant non-protein thiolEpigenetic gene regulationNon-protein thiolsGlutathione S-transferase (GST) familyGene regulationPeroxidase familyExogenous electrophilesCellular methylationReactive oxygen speciesGSH functionsCellular concentrationRelated enzymesTranssulfuration pathwayCancer developmentOxygen speciesBiosynthesisExogenous chemicalsEnzymeTransmethylation pathwayEnhanced susceptibilityPathological conditionsIntimate involvementMillimolar rangePathway
2017
Aldehyde dehydrogenase 1B1: a novel immunohistological marker for colorectal cancer
Matsumoto A, Arcaroli J, Chen Y, Gasparetto M, Neumeister V, Thompson DC, Singh S, Smith C, Messersmith W, Vasiliou V. Aldehyde dehydrogenase 1B1: a novel immunohistological marker for colorectal cancer. British Journal Of Cancer 2017, 117: 1537-1543. PMID: 28881356, PMCID: PMC5680456, DOI: 10.1038/bjc.2017.304.Peer-Reviewed Original ResearchConceptsCRC markersTumor tissueNormal tissuesCell linesHuman CRC explantsCRC cell linesColorectal cancer markersAldehyde dehydrogenase 1A1CRC explantsImmunohistological biomarkersColorectal cancerCRC biomarkersImmunohistological markersTissue microarraySolid tumorsLow expressionMicroarray findingsGenetic alterationsALDH isozymesCell populationsALDH1A1CRCMRNA analysisCancer markersMarkers
2016
Roles of defective ALDH2 polymorphism on liver protection and cancer development
Matsumoto A, Thompson DC, Chen Y, Kitagawa K, Vasiliou V. Roles of defective ALDH2 polymorphism on liver protection and cancer development. Environmental Health And Preventive Medicine 2016, 21: 395-402. PMID: 27714678, PMCID: PMC5112207, DOI: 10.1007/s12199-016-0579-2.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsSerum transaminasesLiver protectionSerum alanine aminotransferase levelsExcessive drinkingAlanine aminotransferase levelsAlcohol-related cancersUseful biological markerAldehyde dehydrogenase 2 geneAminotransferase levelsLiver injuryAlcohol intakeAlcohol dosePotential cancer riskCancer riskALDH2 polymorphismEthanol loadHealthy individualsBiological markersCancer developmentMultiple studiesFurther studiesALDH2TransaminaseDrinkingRiskALDH3A1 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
2015
ALDH1B1 Is Crucial for Colon Tumorigenesis by Modulating Wnt/β-Catenin, Notch and PI3K/Akt Signaling Pathways
Singh S, Arcaroli J, Chen Y, Thompson DC, Messersmith W, Jimeno A, Vasiliou V. ALDH1B1 Is Crucial for Colon Tumorigenesis by Modulating Wnt/β-Catenin, Notch and PI3K/Akt Signaling Pathways. PLOS ONE 2015, 10: e0121648. PMID: 25950950, PMCID: PMC4423958, DOI: 10.1371/journal.pone.0121648.Peer-Reviewed Original ResearchMeSH KeywordsAldehyde DehydrogenaseAldehyde Dehydrogenase 1 FamilyAldehyde Dehydrogenase, MitochondrialAnimalsCell Line, TumorColonic NeoplasmsGene Expression Regulation, NeoplasticHCT116 CellsHT29 CellsHumansMiceNeoplasm TransplantationPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReceptors, NotchRNA, Small InterferingSignal TransductionSpheroids, CellularWnt Signaling PathwayConceptsWnt/β-cateninPI3K/AktΒ-cateninSW-480 cellsColon cancer tumorigenesisWnt reporter activityPattern of expressionPI3K/Akt Signaling PathwayDual-luciferase reporterPI3K/Akt signal pathwayAkt Signaling PathwayTranscription factorsAkt signal pathwayNude mouse xenograft tumor modelColon tumorigenesisGene promoterColon adenocarcinoma cell lineMouse xenograft tumor modelALDH1B1 expressionAldehyde dehydrogenase 1B1Signaling pathwaysLuciferase reporterSize of spheroidsAdenocarcinoma cell lineXenograft tumor model
2014
Transgenic Mouse Models for Alcohol Metabolism, Toxicity, and Cancer
Heit C, Dong H, Chen Y, Shah YM, Thompson DC, Vasiliou V. Transgenic Mouse Models for Alcohol Metabolism, Toxicity, and Cancer. Advances In Experimental Medicine And Biology 2014, 815: 375-387. PMID: 25427919, PMCID: PMC4323349, DOI: 10.1007/978-3-319-09614-8_22.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsReactive oxygen speciesAldehyde dehydrogenasesCritical biological functionsAlcohol dehydrogenaseFormation of proteinHuman genesBiological functionsMolecular mechanismsVariety of cancersPrimary enzymeGenetic defectsOxygen speciesEnzymeNitrogen speciesEthanol metabolismTransgenic mouse modelOxidative stressSpeciesCytochrome P450Pathogenic eventsMetabolismGenetic polymorphismsAntioxidant mechanismsAlcohol-induced toxicityAlcohol-metabolizing enzymes
2013
ALDH16A1 is a novel non-catalytic enzyme that may be involved in the etiology of gout via protein–protein interactions with HPRT1
Vasiliou V, Sandoval M, Backos DS, Jackson BC, Chen Y, Reigan P, Lanaspa MA, Johnson RJ, Koppaka V, Thompson DC. ALDH16A1 is a novel non-catalytic enzyme that may be involved in the etiology of gout via protein–protein interactions with HPRT1. Chemico-Biological Interactions 2013, 202: 22-31. PMID: 23348497, PMCID: PMC3746320, DOI: 10.1016/j.cbi.2012.12.018.Peer-Reviewed Original ResearchConceptsProtein-protein interactionsSingle nucleotide polymorphismsSuch protein-protein interactionsCoiled-coil domainImportant cysteine residuesMissense single nucleotide polymorphismMost mammalian speciesALDH domainHuman cell linesALDH16A1Cysteine residuesMammalian speciesProtein structureUnique memberKey enzymeEtiology of goutGenesNucleotide polymorphismsHPRT activityProteinAcid metabolismCell linesLong formIntriguing possibilityLower animalsThe Role of CYP2E1 in Alcohol Metabolism and Sensitivity in the Central Nervous System
Heit C, Dong H, Chen Y, Thompson DC, Deitrich RA, Vasiliou VK. The Role of CYP2E1 in Alcohol Metabolism and Sensitivity in the Central Nervous System. Subcellular Biochemistry 2013, 67: 235-247. PMID: 23400924, PMCID: PMC4314297, DOI: 10.1007/978-94-007-5881-0_8.ChaptersConceptsCentral nervous systemNervous systemBlood-brain barrierRole of CYP2E1Certain brain cellsCytochrome P450 2E1Particular brain regionsMotor incoordinationBrain barrierSleep inductionEthanol consumptionBrain cellsAlcohol consumptionBrain regionsP450 2E1Alcohol metabolismEthanol metabolismBehavioral effectsCYP2E1Major enzymeLocal productionMetabolismIncoordinationBrain
2012
Aldehyde dehydrogenases in cellular responses to oxidative/electrophilicstress
Singh S, Brocker C, Koppaka V, Chen Y, Jackson BC, Matsumoto A, Thompson DC, Vasiliou V. Aldehyde dehydrogenases in cellular responses to oxidative/electrophilicstress. Free Radical Biology And Medicine 2012, 56: 89-101. PMID: 23195683, PMCID: PMC3631350, DOI: 10.1016/j.freeradbiomed.2012.11.010.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsReactive oxygen speciesOxidative stressMulticellular speciesEukaryotic organismsElectrophilic stressExogenous aldehydesCancer stem cellsLiving systemsStress responseCellular responsesEnvironmental stressorsSimilar functionsAldehyde scavengerSpeciesStem cellsLipid peroxidationROS loadOxygen speciesElevated oxidative stressLipid membranesALDHALDH expressionOrganismsPathological processesPathological conditionsAldehyde dehydrogenases: From eye crystallins to metabolic disease and cancer stem cells
Vasiliou V, Thompson DC, Smith C, Fujita M, Chen Y. Aldehyde dehydrogenases: From eye crystallins to metabolic disease and cancer stem cells. Chemico-Biological Interactions 2012, 202: 2-10. PMID: 23159885, PMCID: PMC4128326, DOI: 10.1016/j.cbi.2012.10.026.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAldehyde dehydrogenaseHuman ALDH genesALDH gene familyNon-catalytic activitiesEukaryotic genomesGene familyALDH genesCancer stem cellsMolecular basisDependent enzymesStem cellsAldehyde metabolismOxidative stressNicotinamide adenine dinucleotideOxidation of aldehydesPathophysiological processesAdenine dinucleotideDehydrogenaseMetabolic diseasesGenomeImportant roleEmbryogenesisGenesStructural elementsCrystallinsOcular aldehyde dehydrogenases: Protection against ultraviolet damage and maintenance of transparency for vision
Chen Y, Thompson DC, Koppaka V, Jester JV, Vasiliou V. Ocular aldehyde dehydrogenases: Protection against ultraviolet damage and maintenance of transparency for vision. Progress In Retinal And Eye Research 2012, 33: 28-39. PMID: 23098688, PMCID: PMC3570594, DOI: 10.1016/j.preteyeres.2012.10.001.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAldehyde dehydrogenasePutative regulatory functionTaxon-specific mannerNon-catalytic functionsRetinoic acid signalingALDH proteinsMaintenance of transparencyCellular transparencyAcid signalingCorneal crystallinsExogenous aldehydesEye developmentOxygen-induced damageCorneal cell proliferationStructural roleRegulatory functionsException of rabbitsMost mammalsRetinaldehyde dehydrogenasesLens crystallinsALDH1A1 proteinMammalian corneaAnimal speciesCell proliferationDependent oxidationALDH1A Isozymes are Markers of Human Melanoma Stem Cells and Potential Therapeutic Targets
Luo Y, Dallaglio K, Chen Y, Robinson WA, Robinson SE, McCarter MD, Wang J, Gonzalez R, Thompson DC, Norris DA, Roop DR, Vasiliou V, Fujita M. ALDH1A Isozymes are Markers of Human Melanoma Stem Cells and Potential Therapeutic Targets. Stem Cells 2012, 30: 2100-2113. PMID: 22887839, PMCID: PMC3448863, DOI: 10.1002/stem.1193.Peer-Reviewed Original ResearchMeSH KeywordsAldehyde DehydrogenaseAldehyde Dehydrogenase 1 FamilyAldehyde OxidoreductasesAnimalsApoptosisCell Transformation, NeoplasticDacarbazineDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticGene SilencingHumansIsoenzymesMelanomaMiceMice, Inbred NODMice, SCIDNeoplasm TransplantationNeoplastic Stem CellsResponse ElementsRetinal DehydrogenaseRNA, Small InterferingSkin NeoplasmsTemozolomideTretinoinConceptsCancer stem cellsPositive melanoma cellsMelanoma cellsTherapeutic targetBiomarkers of CSCsHuman melanomaPatient-derived tumor specimensMelanoma cancer stem cellsNOD/SCID miceALDH-negative cellsHigh aldehyde dehydrogenase (ALDH) activityALDH isozymesNonobese diabetic/Potential therapeutic targetDrug-induced cell deathAttractive therapeutic targetNew molecular targetsHuman melanoma cellsStem cellsMelanoma stem cellsAldehyde dehydrogenase activityHuman melanoma stem cellsNSG miceCell cycle arrestImmunodeficiency miceAldehyde Dehydrogenase Inhibitors: a Comprehensive Review of the Pharmacology, Mechanism of Action, Substrate Specificity, and Clinical Application
Koppaka V, Thompson DC, Chen Y, Ellermann M, Nicolaou KC, Juvonen RO, Petersen D, Deitrich RA, Hurley TD, Vasiliou V. Aldehyde Dehydrogenase Inhibitors: a Comprehensive Review of the Pharmacology, Mechanism of Action, Substrate Specificity, and Clinical Application. Pharmacological Reviews 2012, 64: 520-539. PMID: 22544865, PMCID: PMC3400832, DOI: 10.1124/pr.111.005538.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsRetinoic acid signalingSuperfamily of enzymesCellular defense mechanismsALDH isozymesCellular homeostasisMechanism of actionAcid signalingCorneal crystallinsSubstrate specificityIsozyme-selective inhibitorsALDH enzymesToxicological functionsKey enzymeHuman ALDHHuman diseasesHuman cancersDefense mechanismsPharmacological inhibitionToxicological roleReactive aldehydesALDH inhibitorsIsozymesEnzymeUltraviolet radiation-induced damagePivotal roleMolecular mechanisms of ALDH3A1-mediated cellular protection against 4-hydroxy-2-nonenal
Black W, Chen Y, Matsumoto A, Thompson DC, Lassen N, Pappa A, Vasiliou V. Molecular mechanisms of ALDH3A1-mediated cellular protection against 4-hydroxy-2-nonenal. Free Radical Biology And Medicine 2012, 52: 1937-1944. PMID: 22406320, PMCID: PMC3457646, DOI: 10.1016/j.freeradbiomed.2012.02.050.Peer-Reviewed Original ResearchConceptsAldehyde dehydrogenasesOxidative stress responseCellular defense mechanismsOxidative stressHuman ALDH3A1Proteasome functionMolecular mechanismsPrevents apoptosisStress responseCellular protectionLipid peroxidationAdverse effectsWestern blot analysisAldehydic moleculesGlutathione homeostasisALDH3A1 expressionCell viability assaysMetabolic functionsALDH3A1Blot analysisDefense mechanismsProtein adduct formationCell linesCell viabilityViability assays
2011
Ultraviolet Radiation: Cellular Antioxidant Response and the Role of Ocular Aldehyde Dehydrogenase Enzymes
Marchitti SA, Chen Y, Thompson DC, Vasiliou V. Ultraviolet Radiation: Cellular Antioxidant Response and the Role of Ocular Aldehyde Dehydrogenase Enzymes. Eye & Contact Lens Science & Clinical Practice 2011, 37: 206-213. PMID: 21670692, PMCID: PMC3356694, DOI: 10.1097/icl.0b013e3182212642.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsReactive oxygen speciesCombat reactive oxygen speciesImportant enzymatic antioxidantsAldehyde dehydrogenaseReduction-oxidation homeostasisOxidative damageConstant oxidative stressAldehyde dehydrogenase enzymeCellular antioxidant responseOxidative stressUnique roleCellular membranesCellular responsesAntioxidant defense systemSuperoxide dismutasesAntioxidant responseEnvironmental insultsDownstream effectsDefense systemGlutathione reductaseEnzymatic antioxidantsOxygen speciesDehydrogenase enzymeNicotinamide adenine dinucleotide phosphateNonenzymatic antioxidants