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, PMCID: PMC11500436, 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 studies
2023
A Guide to MALDI Imaging Mass Spectrometry for Tissues
Moore J, Charkoftaki G. A Guide to MALDI Imaging Mass Spectrometry for Tissues. Journal Of Proteome Research 2023, 22: 3401-3417. PMID: 37877579, DOI: 10.1021/acs.jproteome.3c00167.Peer-Reviewed Original ResearchMulti-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 biomarkersHumanized mouse liver reveals endothelial control of essential hepatic metabolic functions
Kaffe E, Roulis M, Zhao J, Qu R, Sefik E, Mirza H, Zhou J, Zheng Y, Charkoftaki G, Vasiliou V, Vatner D, Mehal W, AlcHepNet, Kluger Y, Flavell R. Humanized mouse liver reveals endothelial control of essential hepatic metabolic functions. Cell 2023, 186: 3793-3809.e26. PMID: 37562401, PMCID: PMC10544749, DOI: 10.1016/j.cell.2023.07.017.Peer-Reviewed Original ResearchConceptsMetabolic functionsSpecies-specific interactionsKey metabolic functionsCell-autonomous mechanismsNon-alcoholic fatty liver diseaseMajor metabolic hubNon-parenchymal cellsMetabolic hubHuman hepatocytesMicroenvironmental regulationHuman diseasesHuman-specific aspectsHuman pathologiesHomeostatic processesSpecies mismatchCholesterol uptakeFatty liver diseaseParacrine mannerHuman immuneBile acid conjugationSinusoidal endothelial cellsHepatic metabolic functionMouse liverEndothelial cellsCellsIntegrated Analysis of Tracheobronchial Fluid from Before and After Cardiopulmonary Bypass Reveals Activation of the Integrated Stress Response and Altered Pulmonary Microvascular Permeability
Habet V, Li N, Qi J, Peng G, Charkoftaki G, Vasiliou V, Sharma L, Pober J, Dela Cruz C, Yan X, Pierce R. Integrated Analysis of Tracheobronchial Fluid from Before and After Cardiopulmonary Bypass Reveals Activation of the Integrated Stress Response and Altered Pulmonary Microvascular Permeability. The Yale Journal Of Biology And Medicine 2023, 96: 23-42. PMID: 37009190, PMCID: PMC10052603, DOI: 10.59249/kfyz8002.Peer-Reviewed Original ResearchConceptsIntegrated stress responseProteomic analysisTranscriptional activityStress responseSingle-cell RNA sequencingCell RNA sequencingHuman pulmonary microvascular endothelial cellsMulti-omics approachCell type annotationRespiratory transport chainUnbiased proteomic analysisUpregulation of proteinsIngenuity Pathway AnalysisCardiopulmonary bypassCell clusteringProtective cellular responseFunctional cellular assaysDistinct cell populationsDEG analysisCellular phenotypesRNA sequencingPathway analysisTransport chainCellular responsesImmune cells
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 activityOxidative 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 animalCytotoxicityCYP2E1The Integrated Stress Response Is Upregulated in Pulmonary Structural and Immune Cells After Cardiopulmonary Bypass in Children
Habet V, Li N, Charkoftaki G, Vasiliou V, Yan X, Dela Cruz C, Pierce R. The Integrated Stress Response Is Upregulated in Pulmonary Structural and Immune Cells After Cardiopulmonary Bypass in Children. 2022, a5039-a5039. DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a5039.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 problemMiceLiverLipidomics 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 modelReview of the Third Conference of the Imaging Mass Spectrometry Society (IMSS 3): Accounts of a Hybrid Virtual and In-Person Meeting and the State and Future of the Field
Chandler CE, Anderton CR, Scott AJ, Charkoftaki G, Angel PM, Drake RR. Review of the Third Conference of the Imaging Mass Spectrometry Society (IMSS 3): Accounts of a Hybrid Virtual and In-Person Meeting and the State and Future of the Field. Journal Of The American Society For Mass Spectrometry 2022, 33: 238-241. PMID: 35005981, DOI: 10.1021/jasms.1c00348.Peer-Reviewed Original Research
2021
Population pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide metabolite in patients with autoimmune glomerulonephritis
Iliopoulou VN, Charkoftaki G, Cooper JC, Dokoumetzidis A, Joy MS. Population pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide metabolite in patients with autoimmune glomerulonephritis. Journal Of Pharmacy And Pharmacology 2021, 73: 1683-1692. PMID: 34480477, DOI: 10.1093/jpp/rgab135.Peer-Reviewed Original ResearchConceptsPopulation pharmacokinetic modelPharmacokinetic modelAutoimmune glomerulonephritisCentral volumeSimultaneous population pharmacokinetic modelInitiation of therapyVisual predictive checkProportional error modelElimination rate constantDose regimensPopulation pharmacokineticsTotal clearancePatient variablesPlasma concentrationsCyclophosphamidePharmacokinetic evaluationPharmacokinetic parametersPatientsPlasma samplingPotential covariatesGlomerulonephritisSignificant covariatesPredictive checksFinal modelCovariatesOxidative 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 mechanismsMolecular Mechanisms of Alcohol-Induced Colorectal Carcinogenesis
Johnson CH, Golla JP, Dioletis E, Singh S, Ishii M, Charkoftaki G, Thompson DC, Vasiliou V. Molecular Mechanisms of Alcohol-Induced Colorectal Carcinogenesis. Cancers 2021, 13: 4404. PMID: 34503214, PMCID: PMC8431530, DOI: 10.3390/cancers13174404.Peer-Reviewed Original ResearchColorectal cancerColorectal carcinogenesisChronic alcohol consumptionMost CRC patientsSporadic colorectal cancerGenetic risk factorsEffects of alcoholBacterial translocationCRC patientsFamilial cancer syndromeIntestinal permeabilityRisk factorsAlcohol consumptionCancer syndromesCRC modelMechanisms of alcoholAlcohol metabolitesGermline mutationsOne-carbon metabolismExact mechanismReactive oxygen speciesSporadic cancersCarcinogenesisImmunosuppressionCancerAn evaluation of a novel nanoformulation of imatinib mesylate in a mouse model of lupus nephritis
Fogueri U, Charkoftaki G, Roda G, Tuey S, Ibrahim M, Persaud I, Wempe MF, Brown JM, Thurman JM, Anchordoquy TJ, Joy MS. An evaluation of a novel nanoformulation of imatinib mesylate in a mouse model of lupus nephritis. Drug Delivery And Translational Research 2021, 12: 1445-1454. PMID: 34322850, DOI: 10.1007/s13346-021-01022-4.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosus nephritisKidney depositionImatinib mesylateMouse modelMRL/MpJ miceT-testStudent's t-testDose-toxicity relationshipLupus nephritisSystemic exposureRenal excretionMesangial locationsPharmacokinetic parametersPotential treatmentNaked drugPharmacokineticsNephritisNovel nanoformulationMiceMesylateFuture strategiesCurrent studyNanoformulationsEncouraging resultsKidneyInfluence of vitamin D treatment on functional expression of drug disposition pathways in human kidney proximal tubule cells during simulated uremia
Tuey S, Atilano-Roque A, Charkoftaki G, Thurman J, Nolin T, Joy M. Influence of vitamin D treatment on functional expression of drug disposition pathways in human kidney proximal tubule cells during simulated uremia. Xenobiotica 2021, 51: 657-667. PMID: 33870862, DOI: 10.1080/00498254.2021.1909783.Peer-Reviewed Original ResearchConceptsHuman kidney proximal tubule epithelial cellsUraemic serumProtein expressionHuman kidney proximal tubule cellsVitamin D treatmentEffect of cholecalciferolProximal tubule epithelial cellsKidney proximal tubule epithelial cellsKidney proximal tubule cellsDrug transport pathwaysProximal tubule cellsDrug disposition pathwaysEffect of treatmentTubule epithelial cellsMajor vitamin DVitD treatmentVitamin DFunctional assessmentTubule cellsNM dosesEthanol vehicleFunctional expressionCYP enzymesMRNA expressionDisposition pathwaysEvolution of the liver biopsy and its future
Jain D, Torres R, Celli R, Koelmel J, Charkoftaki G, Vasiliou V. Evolution of the liver biopsy and its future. Translational Gastroenterology And Hepatology 2021, 6: 20-20. PMID: 33824924, PMCID: PMC7829074, DOI: 10.21037/tgh.2020.04.01.Peer-Reviewed Original ResearchLiver biopsyLiver tissueClinical practicePost-transplant complicationsRoutine clinical practiceTissue content analysisCommon indicationLiver diseaseNon-invasive methodMultiphoton microscopyHistologic evaluationMedical disordersEffective treatmentNew therapiesBiopsyClinical diagnosisClinical researchTissue samplesVisualization of tissuesTissue sectionsPrognostic capabilityClinical workflowImproved clinical diagnosisTissueDiagnosisIdentification 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 studyNetwork machine learning maps phytochemically rich “Hyperfoods” to fight COVID-19
Laponogov I, Gonzalez G, Shepherd M, Qureshi A, Veselkov D, Charkoftaki G, Vasiliou V, Youssef J, Mirnezami R, Bronstein M, Veselkov K. Network machine learning maps phytochemically rich “Hyperfoods” to fight COVID-19. Human Genomics 2021, 15: 1. PMID: 33386081, PMCID: PMC7775839, DOI: 10.1186/s40246-020-00297-x.Peer-Reviewed Original Research