Ying Chen, MD, PhD
Research Scientist in Epidemiology (Environmental Health Sciences)Cards
About
Research
Overview
Dr. Chen’s research focuses on understanding the mechanistic functions of redox homeostasis and antioxidant deficiencies in human diseases associated with environmental and dietary stress. Reduced GSH is the most abundant thiol antioxidant that combats excessive oxidants generated during cellular metabolism or in response to environmental assaults. GSH deficiency has been associated with numerous pathological conditions in human. Dr. Chen’s research work involves the use of unique redox animal models and system biology approach to elucidate the molecular mechanisms underlying liver diseases and neurological disorders.
Specific research projects include:
- Redox-mediated mechanisms in protection against alcohol-associated fatty liver disease
- The mechanistic role of oxidative stress in water contaminant 1,4-dioxane-induced liver cytotoxicity and genotoxicity
- The functional interplay between two antioxidants (glutathione and ascorbate) in the central nervous system
Medical Research Interests
Digestive System Diseases; Disorders of Environmental Origin; Nervous System Diseases; Nutritional and Metabolic Diseases
Public Health Interests
Cancer; Environmental Health; Genetics, Genomics, Epigenetics; Metabolomics
Publications
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 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 exposure
Academic Achievements & Community Involvement
News
News
- August 08, 2016
Yale Research Provides Insights into Alcoholic Liver Disease
- February 01, 2016
The Threat of Lead
- September 06, 2011Source: The Denver Post
CU research: Enzyme discovered that could detect colon cancer earlier
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Environmental Health Sciences
60 College St, LEPH 521
New Haven, CT 06520
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60 College Street, Fl 5th, Rm 508
New Haven, CT 06510
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