2023
Humanized 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 cellsCells
2022
Liver 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 model
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 mechanismsAn 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 resultsKidneyIdentification 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
2019
Update 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
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 effectsDamageInjuryPathway