Featured Publications
Mitochondrial DNA and the STING pathway are required for hepatic stellate cell activation
Arumugam S, Li B, Boodapati S, Nathanson M, Sun B, Ouyang X, Mehal W. Mitochondrial DNA and the STING pathway are required for hepatic stellate cell activation. Hepatology 2023, 78: 1448-1461. PMID: 37013923, PMCID: PMC10804318, DOI: 10.1097/hep.0000000000000388.Peer-Reviewed Original ResearchConceptsVoltage-dependent anion channelBioenergetic capacityMitochondrial DNATranscriptional upregulationCyclic GMP-AMP synthaseGMP-AMP synthaseTranscriptional regulationBioenergetic organellesFunctional mitochondriaMitochondrial membraneExternal mitochondrial membraneAnabolic pathwaysMitochondrial massAnion channelInterferon genesHSC transdifferentiationSubsequent activationCGAS-STINGTransdifferentiationIRF3 pathwayPathwaySTING pathwayGenesMitochondriaQuiescent HSCsGSK3β mediates the spatiotemporal dynamics of NLRP3 inflammasome activation
Arumugam S, Qin Y, Liang Z, Han SN, Boodapati SLT, Li J, Lu Q, Flavell RA, Mehal WZ, Ouyang X. GSK3β mediates the spatiotemporal dynamics of NLRP3 inflammasome activation. Cell Death & Differentiation 2022, 29: 2060-2069. PMID: 35477991, PMCID: PMC9525599, DOI: 10.1038/s41418-022-00997-y.Peer-Reviewed Original ResearchConceptsInflammasome assemblyGlycogen synthase kinase-3βSynthase kinase-3βOrganelle dynamicsGolgi networkSubcellular machineryGolgi apparatusInflammasome activationMechanistic basisKinase-3βMolecular determinantsSpatiotemporal dynamicsGSK3β activationMitochondriaNLRP3 oligomerizationTGNSubsequent bindingGSK3βNLRP3 inflammasome activationActivationNew avenuesAssemblyStepwise processOrganellesPhosphatidylinositolm6A mRNA methylation-directed myeloid cell activation controls progression of NAFLD and obesity
Qin Y, Li B, Arumugam S, Lu Q, Mankash SM, Li J, Sun B, Li J, Flavell RA, Li HB, Ouyang X. m6A mRNA methylation-directed myeloid cell activation controls progression of NAFLD and obesity. Cell Reports 2021, 37: 109968. PMID: 34758326, PMCID: PMC8667589, DOI: 10.1016/j.celrep.2021.109968.Peer-Reviewed Original ResearchConceptsNon-alcoholic fatty liver diseaseProgression of NAFLDLineage-restricted deletionFatty liver diseaseMultiple mRNA transcriptsMyeloid cell activationDiet-induced developmentMethyladenosine (m<sup>6</sup>A) RNA modificationMRNA metabolismProtein methyltransferaseLiver diseaseRNA modificationsCellular stressMetabolic reprogrammingDDIT4 mRNACell activationObesityDifferential expressionMammalian targetMRNA transcriptsSignificant downregulationCytokine stimulationPathway activityMetabolic phenotypeMRNA levelsTargeting glycogen synthase kinase-3β inhibition alleviates acute myocardial infarction through reduction of NLRP3 inflammasome activation
Wang S, Xu L, Chang C, Yao Y, Su X, Cha X, Komal S, Wang P, Ouyang X, ZHANG L, Han S. Targeting glycogen synthase kinase-3β inhibition alleviates acute myocardial infarction through reduction of NLRP3 inflammasome activation. Journal Of Molecular And Cellular Cardiology 2020, 140: 38-39. DOI: 10.1016/j.yjmcc.2019.11.091.Peer-Reviewed Original ResearchDigoxin improves steatohepatitis with differential involvement of liver cell subsets in mice through inhibition of PKM2 transactivation
Zhao P, Han SN, Arumugam S, Yousaf MN, Qin Y, Jiang JX, Torok NJ, Chen Y, Mankash MS, Liu J, Li J, Iwakiri Y, Ouyang X. Digoxin improves steatohepatitis with differential involvement of liver cell subsets in mice through inhibition of PKM2 transactivation. AJP Gastrointestinal And Liver Physiology 2019, 317: g387-g397. PMID: 31411894, PMCID: PMC6842989, DOI: 10.1152/ajpgi.00054.2019.Peer-Reviewed Original ResearchConceptsHigh-fat dietSignificant clinical applicabilityHuman nonalcoholic steatohepatitisNonalcoholic steatohepatitisOral digoxinLiver injuryCell subsetsPathway activationMouse modelHigh-fat diet mouse modelLiver injury mouse modelHepatocyte mitochondrial dysfunctionClinical applicabilityDiet mouse modelInjury mouse modelDifferential involvementLarge clinical experienceNLRP3 inflammasome activationSignificant protective effectHIF-1α transactivationHepatic oxidative stress responseHypoxia-inducible factorLiver inflammationHFD miceWide dosage rangeDigoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1α Transactivation in Steatohepatitis
Ouyang X, Han SN, Zhang JY, Dioletis E, Nemeth BT, Pacher P, Feng D, Bataller R, Cabezas J, Stärkel P, Caballeria J, Pongratz RL, Cai SY, Schnabl B, Hoque R, Chen Y, Yang WH, Garcia-Martinez I, Wang FS, Gao B, Torok NJ, Kibbey RG, Mehal WZ. Digoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1α Transactivation in Steatohepatitis. Cell Metabolism 2018, 27: 339-350.e3. PMID: 29414684, PMCID: PMC5806149, DOI: 10.1016/j.cmet.2018.01.007.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCell NucleusChromatinDigoxinDisease Models, AnimalEndotoxinsHistonesHumansHypoxia-Inducible Factor 1, alpha SubunitInflammationLiverNon-alcoholic Fatty Liver DiseaseOxidation-ReductionProtein BindingPyruvate KinaseTHP-1 CellsTranscription, GeneticTranscriptional ActivationConceptsHIF-1α transactivationSterile inflammationHIF-1α pathway activationNon-alcoholic steatohepatitisKinase M2Major clinical consequencesAbility of digoxinLiver inflammationLiver diseasePyruvate kinase M2Clinical consequencesTherapeutic targetInflammationTissue damageHIF-1αPathway activationDigoxinOxidative stressCardiac glycosidesSteatohepatitisDigoxin bindsNovel roleLiverUbiquitous responseActivationDigoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1α Transactivation in Steatohepatitis
Ouyang X, Han SN, Zhang JY, Dioletis E, Nemeth BT, Pacher P, Feng D, Bataller R, Cabezas J, Stärkel P, Caballeria J, Pongratz R, Cai SY, Schnabl B, Hoque R, Chen Y, Yang WH, Garcia-Martinez I, Wang FS, Gao B, Torok NJ, Kibbey RG, Mehal WZ. Digoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1α Transactivation in Steatohepatitis. Cell Metabolism 2018, 27: 1156. PMID: 29719229, DOI: 10.1016/j.cmet.2018.04.007.Peer-Reviewed Original ResearchThe DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury
Hu B, Jin C, Li HB, Tong J, Ouyang X, Cetinbas NM, Zhu S, Strowig T, Lam FC, Zhao C, Henao-Mejia J, Yilmaz O, Fitzgerald KA, Eisenbarth SC, Elinav E, Flavell RA. The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury. Science 2016, 354: 765-768. PMID: 27846608, PMCID: PMC5640175, DOI: 10.1126/science.aaf7532.Peer-Reviewed Original ResearchConceptsCell deathDNA sensor AIM2New therapeutic targetsCaspase-1-dependent deathIntestinal epithelial cellsBone marrow cellsGastrointestinal syndromeTissue injuryInflammasome activationGastrointestinal tractRadiation-induced cell deathRadiation-induced DNA damageTherapeutic targetAcute exposureBone marrowChemotherapeutic agentsMarrow cellsRadiation exposureAIM2Massive cell deathEpithelial cellsHematopoietic failureDeathMolecular mechanismsDNA damageAdenosine is required for sustained inflammasome activation via the A2A receptor and the HIF-1α pathway
Ouyang X, Ghani A, Malik A, Wilder T, Colegio OR, Flavell RA, Cronstein BN, Mehal WZ. Adenosine is required for sustained inflammasome activation via the A2A receptor and the HIF-1α pathway. Nature Communications 2013, 4: 2909. PMID: 24352507, PMCID: PMC3895487, DOI: 10.1038/ncomms3909.Peer-Reviewed Original ResearchMeSH KeywordsAdenosineAdenosine TriphosphateAnimalsCarrier ProteinsCyclic AMPCyclic AMP Response Element-Binding ProteinCyclic AMP-Dependent Protein KinasesHypoxia-Inducible Factor 1, alpha SubunitInflammasomesInterleukin-1betaLipopolysaccharidesLiverMacrophagesMaleMiceMice, Inbred C57BLNLR Family, Pyrin Domain-Containing 3 ProteinReceptor, Adenosine A2ASignal TransductionConceptsHIF-1α pathwayInflammasome activityInflammasome activationA2A receptorsIL-1β productionIL-1β responseReceptor-mediated signalingLack of responseTolerogenic stateChronic diseasesInflammatory responseInflammasome pathwayPrevious exposureLipopolysaccharideAdenosineReceptorsActivationKey regulatorInitial activationPathwaySignalingResponseInterleukinStimuliDisease
2024
RNA modifications in the progression of liver diseases: from fatty liver to cancer
Li S, Mehal W, Ouyang X. RNA modifications in the progression of liver diseases: from fatty liver to cancer. Science China Life Sciences 2024, 67: 2105-2119. PMID: 38809498, DOI: 10.1007/s11427-023-2494-x.Peer-Reviewed Original ResearchRNA modificationsRNA metabolismRNA speciesNon-alcoholic fatty liver diseaseN1-methyladenosineCellular functionsN6-methyladenosineGene expressionRNANon-alcoholic steatohepatitisFatty liver to non-alcoholic steatohepatitisM6AHepatocellular carcinomaGlobal health concernFatty liver diseaseLiver diseaseM5CHigher risk of metabolic syndromePseudouridineAssociated with higher risk of metabolic syndromePathological conditionsRisk of metabolic syndromeGenes-methyladenosineProgression of liver diseaseComplement protein signatures in patients with alcohol-associated hepatitis
Taiwo M, Huang E, Pathak V, Bellar A, Welch N, Dasarathy J, Streem D, McClain C, Mitchell M, Barton B, Szabo G, Dasarathy S, Consortium A, Schaefer E, Luther J, Day L, Ouyang X, Suyavaran A, Mehal W, Jacobs J, Goodman R, Rotroff D, Nagy L. Complement protein signatures in patients with alcohol-associated hepatitis. JCI Insight 2024, 9: e174127. PMID: 38573776, PMCID: PMC11141929, DOI: 10.1172/jci.insight.174127.Peer-Reviewed Original ResearchAlcohol-associated hepatitisSevere AHAlcohol use disorderAlcoholic cirrhosisHealthy controlsPredicting 90-day mortalityComplement proteinsSerum proteome of patientsEthanol-induced liver injurySerum proteomeDevelopment of effective therapiesProteome of patientsAssociated with pro-inflammatory cytokinesProtein signaturesPro-inflammatory cytokinesCoagulation factors IINon-invasive biomarkersDiagnostic challengeSerine protease 1Murine modelEffective therapyLiver injuryPrognostic biomarkerHepatic inflammationC1q binding protein
2023
An analysis of the nutritional effects of Schisandra chinensis components based on mass spectrometry technology
Jia M, Zhou L, Lou Y, Yang X, Zhao H, Ouyang X, Huang Y. An analysis of the nutritional effects of Schisandra chinensis components based on mass spectrometry technology. Frontiers In Nutrition 2023, 10: 1227027. PMID: 37560060, PMCID: PMC10408133, DOI: 10.3389/fnut.2023.1227027.Peer-Reviewed Original ResearchNew uses for an old remedy: Digoxin as a potential treatment for steatohepatitis and other disorders
Jamshed F, Dashti F, Ouyang X, Mehal W, Banini B. New uses for an old remedy: Digoxin as a potential treatment for steatohepatitis and other disorders. World Journal Of Gastroenterology 2023, 29: 1824-1837. PMID: 37032732, PMCID: PMC10080697, DOI: 10.3748/wjg.v29.i12.1824.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2022
Digoxin as an emerging therapy in noncardiac diseases
Dashti F, Jamshed F, Ouyang X, Mehal W, Banini B. Digoxin as an emerging therapy in noncardiac diseases. Trends In Pharmacological Sciences 2022, 44: 199-203. PMID: 36396496, DOI: 10.1016/j.tips.2022.10.002.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsRNA m6A demethylase ALKBH5 regulates the development of γδ T cells
Ding C, Xu H, Yu Z, Roulis M, Qu R, Zhou J, Oh J, Crawford J, Gao Y, Jackson R, Sefik E, Li S, Wei Z, Skadow M, Yin Z, Ouyang X, Wang L, Zou Q, Su B, Hu W, Flavell RA, Li HB. RNA m6A demethylase ALKBH5 regulates the development of γδ T cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2203318119. PMID: 35939687, PMCID: PMC9388086, DOI: 10.1073/pnas.2203318119.Peer-Reviewed Original ResearchConceptsDemethylase ALKBH5Messenger RNAΓδ T cellsΓδ T cell biologyCommon posttranscriptional modificationΓδ T cell developmentT cell biologyT cell developmentCell precursorsT cell precursorsMammalian cellsRNA modificationsPosttranscriptional modificationsTissue homeostasisCell biologyT cellsTarget genesCheckpoint roleCell developmentM6A demethylase ALKBH5ALKBH5Γδ T-cell originΓδ T cell repertoireCell populationsEarly developmentSEMA7AR148W mutation promotes lipid accumulation and NAFLD progression via increased localization on the hepatocyte surface
Zhao N, Zhang X, Ding J, Pan Q, Zheng MH, Liu WY, Luo G, Qu J, Li M, Li L, Cheng Y, Peng Y, Xie Q, Wei Q, Li Q, Zou L, Ouyang X, Cai SY, Boyer JL, Chai J. SEMA7AR148W mutation promotes lipid accumulation and NAFLD progression via increased localization on the hepatocyte surface. JCI Insight 2022, 7: e154113. PMID: 35938531, PMCID: PMC9462498, DOI: 10.1172/jci.insight.154113.Peer-Reviewed Original ResearchConceptsIntegrin β1Lipid accumulationPrimary mouse hepatocytesProtein interactionsLipid droplet accumulationMouse liverFatty acid oxidationHeterozygous mutationsIntegrin β1 proteinPKC-α phosphorylationFA uptakeGenetic determinantsMouse peritoneal macrophagesCell membraneStrong genetic determinantsMutationsMouse hepatocytesDroplet accumulationΒ1 proteinCD36 expressionAcid oxidationPKCTriglyceride synthesisGenetic polymorphismsAccumulationFermented Soy Drink (Q-CAN® PLUS) Induces Apoptosis and Reduces Viability of Cancer Cells
Ouyang X, Chen Y, Tejaswi BS, Arumugam S, Secor E, Weiss TR, Leapman M, Ali A. Fermented Soy Drink (Q-CAN® PLUS) Induces Apoptosis and Reduces Viability of Cancer Cells. Nutrition And Cancer 2022, 74: 3670-3678. PMID: 35603899, PMCID: PMC10986312, DOI: 10.1080/01635581.2022.2077385.Peer-Reviewed Original ResearchAnnexin A2: The diversity of pathological effects in tumorigenesis and immune response
Huang Y, Jia M, Yang X, Han H, Hou G, Bi L, Yang Y, Zhang R, Zhao X, Peng C, Ouyang X. Annexin A2: The diversity of pathological effects in tumorigenesis and immune response. International Journal Of Cancer 2022, 151: 497-509. PMID: 35474212, DOI: 10.1002/ijc.34048.Peer-Reviewed Original ResearchConceptsImmune responseAnnexin A2Pathological effectsToll-like receptor 2Anti-dsDNA antibodiesAcute promyelocytic leukemiaImmune host responseVariety of tumorsEpithelial-mesenchymal transitionInhibition of invasionTumor drug resistanceMultiple tumor cellsInflammatory factorsPathophysiologic processesG1-S phaseRetinal angiogenesisPromyelocytic leukemiaReceptor 2Production of plasminTumor cell invasionHost responseMultiple signal pathwaysNumerous malignanciesDrug resistanceTumor cellsRevisiting the Principles of Preservation in an Era of Pandemic Obesity
Langford JT, DiRito JR, Doilicho N, Chickering GR, Stern DA, Ouyang X, Mehal W, Tietjen GT. Revisiting the Principles of Preservation in an Era of Pandemic Obesity. Frontiers In Immunology 2022, 13: 830992. PMID: 35432296, PMCID: PMC9011385, DOI: 10.3389/fimmu.2022.830992.Peer-Reviewed Original ResearchConceptsDeceased donorsOrgan preservationDonor populationIschemia-reperfusion injuryCurrent obesity epidemicHealthy donor populationPandemic obesityObese donorsReperfusion injuryMetabolic dysfunctionObesity epidemicObesitySignificant declineOrgansDonorsPopulationCurrent practiceDysfunctionTransplantInjury
2021
A digital pathology tool for quantification of color features in histologic specimens
Reschke M, DiRito JR, Stern D, Day W, Plebanek N, Harris M, Hosgood SA, Nicholson ML, Haakinson DJ, Zhang X, Mehal WZ, Ouyang X, Pober JS, Saltzman WM, Tietjen GT. A digital pathology tool for quantification of color features in histologic specimens. Bioengineering & Translational Medicine 2021, 7: e10242. PMID: 35111944, PMCID: PMC8780932, DOI: 10.1002/btm2.10242.Peer-Reviewed Original ResearchTissue samplesColor featuresPathologic featuresDistinct color featuresTissue-based analysisHistologic specimensDigital pathology toolsHistologic samplesExperienced pathologistsImage analysis algorithmsHistologic sectionsPreclinical researchHistological analysisHistological samplesImage analysis toolsCryopreserved tissuesColor thresholdingBetter rigorAnalysis algorithmPathology toolsAnalysis toolsClear needImage assessmentWhole sampleHand tracing