2022
Mechanotransduction-induced glycolysis epigenetically regulates a CXCL1-dominant angiocrine signaling program in liver sinusoidal endothelial cells in vitro and in vivo
Greuter T, Yaqoob U, Gan C, Jalan-Sakrikar N, Kostallari E, Lu J, Gao J, Sun L, Liu M, Sehrawat TS, Ibrahim SH, Furuta K, Nozickova K, Huang BQ, Gao B, Simons M, Cao S, Shah VH. Mechanotransduction-induced glycolysis epigenetically regulates a CXCL1-dominant angiocrine signaling program in liver sinusoidal endothelial cells in vitro and in vivo. Journal Of Hepatology 2022, 77: 723-734. PMID: 35421427, PMCID: PMC9391258, DOI: 10.1016/j.jhep.2022.03.029.Peer-Reviewed Original ResearchConceptsFocal adhesionsGlycolytic enzymesIsolated focal adhesionsChromosome conformation captureHistone activation marksChromatin immunoprecipitation analysisConformation captureChIP sequencingActivation marksEpigenetic regulationActin dynamicsHistone acetylationRNA sequencingERT2 miceActin polymerizationEndothelial cellsCXCL1 promoterNovel roleIntegrin β1Druggable targetsInhibition of glycolysisNuclear chromatinGlycolysisAngiocrineEnzyme
2021
Super enhancer regulation of cytokine-induced chemokine production in alcoholic hepatitis
Liu M, Cao S, He L, Gao J, Arab J, Cui H, Xuan W, Gao Y, Sehrawat T, Hamdan F, Ventura-Cots M, Argemi J, Pomerantz W, Johnsen S, Lee J, Gao F, Ordog T, Mathurin P, Revzin A, Bataller R, Yan H, Shah V. Super enhancer regulation of cytokine-induced chemokine production in alcoholic hepatitis. Nature Communications 2021, 12: 4560. PMID: 34315876, PMCID: PMC8316465, DOI: 10.1038/s41467-021-24843-w.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChemokinesCytokinesDisease Models, AnimalEndothelial CellsEnhancer Elements, GeneticEpigenesis, GeneticGene Expression RegulationHepatitis, AlcoholicHistonesHumansLipopolysaccharidesLiverMice, Inbred C57BLNeutrophilsNF-kappa BPromoter Regions, GeneticRNA-SeqSignal TransductionTranscription FactorsTumor Necrosis Factor-alphaConceptsAlcoholic hepatitisLiver sinusoidal endothelial cellsChemokine expressionNeutrophil infiltrationLiver neutrophil infiltrationTNFα/NF-κB signalingNF-κB signalingHuman liver explantsElevated chemokine expressionSinusoidal endothelial cellsCXCL expressionChemokine productionCXCL chemokinesCytokine pathwaysCytokines TNFαInflammatory signalingMurine modelLiver explantsTherapeutic potentialPharmacologic inhibitionExtraterminal (BET) proteinsBET inhibitionHuman liverEndothelial cellsAH treatmentEndothelial p300 Promotes Portal Hypertension and Hepatic Fibrosis Through C‐C Motif Chemokine Ligand 2–Mediated Angiocrine Signaling
Gao J, Wei B, Liu M, Hirsova P, Sehrawat T, Cao S, Hu X, Xue F, Yaqoob U, Kang N, Cui H, Pomerantz W, Kostallari E, Shah V. Endothelial p300 Promotes Portal Hypertension and Hepatic Fibrosis Through C‐C Motif Chemokine Ligand 2–Mediated Angiocrine Signaling. Hepatology 2021, 73: 2468-2483. PMID: 33159815, PMCID: PMC8102654, DOI: 10.1002/hep.31617.Peer-Reviewed Original ResearchConceptsLiver sinusoidal endothelial cellsPartial inferior vena cava ligationPortal hypertensionLiver fibrosisLiver injuryMacrophage accumulationCCL2 transcriptionKnockout miceC motif chemokine ligand 2Inferior vena cava ligationP50 knockout miceNuclear factor kappa BVena cava ligationChemokine ligand 2Accumulation of macrophagesPathological inflammatory responsesWild-type miceFactor kappa BSinusoidal endothelial cellsInhibition of p300CCL2 deficiencyPortal pressureLiver diseaseInflammatory cellsCCL2 expressionRegulation and functional roles of chemokines in liver diseases
Cao S, Liu M, Sehrawat T, Shah V. Regulation and functional roles of chemokines in liver diseases. Nature Reviews Gastroenterology & Hepatology 2021, 18: 630-647. PMID: 33976393, PMCID: PMC9036964, DOI: 10.1038/s41575-021-00444-2.Peer-Reviewed Original ResearchConceptsLiver diseaseImmune cellsAlcohol-associated liver diseaseOngoing clinical trialsRelevant preclinical studiesFunction of chemokinesLiver infiltrationChemokine transcriptionNonalcoholic steatohepatitisChemokine productionCell-type specific productionClinical trialsInflammatory responseFunctional rolePreclinical studiesChemokine functionAnimal modelsChemokinesChemokine biologyLiver homeostasisTherapeutic opportunitiesDiseaseLiver cellsCellsWeight proteinsCirculating Extracellular Vesicles Carrying Sphingolipid Cargo for the Diagnosis and Dynamic Risk Profiling of Alcoholic Hepatitis
Sehrawat T, Arab J, Liu M, Amrollahi P, Wan M, Fan J, Nakao Y, Pose E, Navarro‐Corcuera A, Dasgupta D, Liao C, He L, Mauer A, Avitabile E, Ventura‐Cots M, Bataller R, Sanyal A, Chalasani N, Heimbach J, Watt K, Gores G, Gines P, Kamath P, Simonetto D, Hu T, Shah V, Malhi H. Circulating Extracellular Vesicles Carrying Sphingolipid Cargo for the Diagnosis and Dynamic Risk Profiling of Alcoholic Hepatitis. Hepatology 2021, 73: 571-585. PMID: 32246544, PMCID: PMC7541595, DOI: 10.1002/hep.31256.Peer-Reviewed Original ResearchConceptsEnd-stage liver diseaseAlcohol-associated cirrhosisAlcoholic hepatitisAH subjectsHealthy controlsHeavy drinkersLiver diseaseEtiology of ESLDEV concentrationEnd-stage liver disease (MELD) scoreExtracellular vesiclesRisk profilingPathogenesis of AHLiver Disease scoreCholestatic liver diseaseNonalcoholic steatohepatitisRisk stratificationClinical criteriaPrognostic performanceDisease scoreDiagnostic biomarkersDisease controlEV countsDiseaseDrinkers
2020
Alcohol-Associated Liver Disease
Liu M, Sehrawat T, Szabo G, Shah V. Alcohol-Associated Liver Disease. 2020, 309-324. DOI: 10.1007/978-3-030-51709-0_20.Peer-Reviewed Original ResearchHyperammonemic Encephalopathy Exacerbated by Parenteral Nutrition in Fibrolamellar Hepatocellular Carcinoma
Shah P, Cho J, Albitar H, Pajot G, Liu M, Ravi K. Hyperammonemic Encephalopathy Exacerbated by Parenteral Nutrition in Fibrolamellar Hepatocellular Carcinoma. The American Journal Of Medicine 2020, 133: e745-e746. PMID: 32739410, DOI: 10.1016/j.amjmed.2020.06.022.Peer-Reviewed Original ResearchEsophageal Varices: Primary Prophylaxis and Prevention and Management of Rebleeding
Liu M, Hilscher M, Kamath P. Esophageal Varices: Primary Prophylaxis and Prevention and Management of Rebleeding. Current Hepatology Reports 2020, 19: 213-225. DOI: 10.1007/s11901-020-00525-x.Peer-Reviewed Original ResearchPortal hypertensionGastroesophageal variceal hemorrhageChronic liver diseaseManagement of patientsPrimary prophylaxisVariceal hemorrhageGastric varicesSecondary preventionAcute managementLiver diseaseRisk stratificationHigh morbidityPrimary preventionPatient outcomesClinical studiesDifferential diagnosisHypertensionDiagnostic criteriaNatural historySummaryThis reviewPreventionVaricesImportant manifestationFurther researchRebleedingIRE1A Stimulates Hepatocyte-Derived Extracellular Vesicles That Promote Inflammation in Mice With Steatohepatitis
Dasgupta D, Nakao Y, Mauer A, Thompson J, Sehrawat T, Liao C, Krishnan A, Lucien F, Guo Q, Liu M, Xue F, Fukushima M, Katsumi T, Bansal A, Pandey M, Maiers J, DeGrado T, Ibrahim S, Revzin A, Pavelko K, Barry M, Kaufman R, Malhi H. IRE1A Stimulates Hepatocyte-Derived Extracellular Vesicles That Promote Inflammation in Mice With Steatohepatitis. Gastroenterology 2020, 159: 1487-1503.e17. PMID: 32574624, PMCID: PMC7666601, DOI: 10.1053/j.gastro.2020.06.031.Peer-Reviewed Original ResearchConceptsX-box binding protein 1Release of EVsHepatocyte-derived extracellular vesiclesSerine palmitoyltransferase genesExtracellular vesiclesSerine palmitoyltransferaseChromatin immunoprecipitationCeramide biosynthesisInflammatory Extracellular VesiclesMonocyte-derived macrophagesUnfolded protein responseNonalcoholic steatohepatitisDiet-induced steatohepatitisGene expression analysisPrimary hepatocytesNumber of EVsBinding protein 1Cultured primary hepatocytesNanoparticle-tracking analysisNanoscale flow cytometryIRE1ALiver tissueRate-limiting enzymeProtein responseExpression analysisThe knowns and unknowns of treatment for alcoholic hepatitis
Sehrawat T, Liu M, Shah V. The knowns and unknowns of treatment for alcoholic hepatitis. The Lancet Gastroenterology & Hepatology 2020, 5: 494-506. PMID: 32277902, PMCID: PMC7238289, DOI: 10.1016/s2468-1253(19)30326-7.Peer-Reviewed Original ResearchConceptsAlcoholic hepatitisLiver diseaseSevere alcoholic hepatitisInflammatory liver diseaseChronic liver diseaseOngoing clinical trialsEffective medical treatmentMedical therapyHigh morbidityClinical trialsHepatitisPreclinical studiesNew therapiesRapid onsetMedical treatmentMyriad complicationsEffective therapeuticsModest effectivenessAlcohol dependencySeries paperPatientsTherapyDiseaseTreatmentLong term
2019
Author Correction: Sustained perfusion of revascularized bioengineered livers heterotopically transplanted into immunosuppressed pigs
Shaheen M, Joo D, Ross J, Anderson B, Chen H, Huebert R, Li Y, Amiot B, Young A, Zlochiver V, Nelson E, Mounajjed T, Dietz A, Michalak G, Steiner B, Davidow D, Paradise C, van Wijnen A, Shah V, Liu M, Nyberg S. Author Correction: Sustained perfusion of revascularized bioengineered livers heterotopically transplanted into immunosuppressed pigs. Nature Biomedical Engineering 2019, 4: 476-476. PMID: 31690827, DOI: 10.1038/s41551-019-0483-3.Peer-Reviewed Original ResearchIn Reply: Beta-Blocker Use in Refractory Ascites
Liu M, Simonetto D. In Reply: Beta-Blocker Use in Refractory Ascites. Mayo Clinic Proceedings 2019, 94: 2364-2365. PMID: 31685161, DOI: 10.1016/j.mayocp.2019.09.009.Peer-Reviewed Original ResearchSustained perfusion of revascularized bioengineered livers heterotopically transplanted into immunosuppressed pigs
Shaheen M, Joo D, Ross J, Anderson B, Chen H, Huebert R, Li Y, Amiot B, Young A, Zlochiver V, Nelson E, Mounajjed T, Dietz A, Michalak G, Steiner B, Davidow D, Paradise C, van Wijnen A, Shah V, Liu M, Nyberg S. Sustained perfusion of revascularized bioengineered livers heterotopically transplanted into immunosuppressed pigs. Nature Biomedical Engineering 2019, 4: 437-445. PMID: 31611679, PMCID: PMC7153989, DOI: 10.1038/s41551-019-0460-x.Peer-Reviewed Original ResearchConceptsHuman endothelial cellsEndothelial cellsSustained perfusionImmune responseContinuous perfusionNormal liver tissueHuman umbilical vein endothelial cellsUmbilical vein endothelial cellsImmunosuppression protocolsAnticoagulation therapyVein endothelial cellsImmunosuppressed pigsEndothelial markersLiver sinusoidsPerfusionLiver tissueHuman liverLiverBlood perfusionHeterotopic implantationMain predictorsLiver scaffoldsPigsPorcine liverDays239 – Mechanotransduction-Induced Glycolysis Epigenetically Regulates a Cxcl1-Dominant Angiocrine Signaling Program in Liver Sinusoidal Endothelial Cells
Greuter T, Yaqoob U, Liu M, Huang B, Cao S, Sh V. 239 – Mechanotransduction-Induced Glycolysis Epigenetically Regulates a Cxcl1-Dominant Angiocrine Signaling Program in Liver Sinusoidal Endothelial Cells. Gastroenterology 2019, 156: s-1184. DOI: 10.1016/s0016-5085(19)39932-9.Peer-Reviewed Original ResearchNew Prospects for Medical Management of Acute Alcoholic Hepatitis
Liu M, Shah V. New Prospects for Medical Management of Acute Alcoholic Hepatitis. Clinical Liver Disease 2019, 13: 131-135. PMID: 31236260, PMCID: PMC6544414, DOI: 10.1002/cld.792.Peer-Reviewed Original ResearchPortal Hypertension and Related Complications: Diagnosis and Management
Simonetto D, Liu M, Kamath P. Portal Hypertension and Related Complications: Diagnosis and Management. Mayo Clinic Proceedings 2019, 94: 714-726. PMID: 30947834, DOI: 10.1016/j.mayocp.2018.12.020.Peer-Reviewed Original ResearchMechanical Stretch Increases Expression of CXCL1 in Liver Sinusoidal Endothelial Cells to Recruit Neutrophils, Generate Sinusoidal Microthombi, and Promote Portal Hypertension
Hilscher M, Sehrawat T, Arab J, Zeng Z, Gao J, Liu M, Kostallari E, Gao Y, Simonetto D, Yaqoob U, Cao S, Revzin A, Beyder A, Wang R, Kamath P, Kubes P, Shah V. Mechanical Stretch Increases Expression of CXCL1 in Liver Sinusoidal Endothelial Cells to Recruit Neutrophils, Generate Sinusoidal Microthombi, and Promote Portal Hypertension. Gastroenterology 2019, 157: 193-209.e9. PMID: 30872106, PMCID: PMC6581607, DOI: 10.1053/j.gastro.2019.03.013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium SignalingCapillariesChemokine CXCL1Endothelial CellsExtracellular TrapsHydrolasesHypertension, PortalIn Vitro TechniquesIntegrinsLeukocyte ElastaseLigationLiverMechanotransduction, CellularMiceMice, Inbred C57BLMice, KnockoutNeutrophil InfiltrationPortal PressureProtein-Arginine Deiminase Type 4Receptor, Notch1Stress, MechanicalThrombosisVena Cava, InferiorConceptsLiver sinusoidal endothelial cellsPortal hypertensionBile duct ligationPortal pressureSinusoidal endothelial cellsFormation of NETsPrimary liver sinusoidal endothelial cellsMechanical stretchControl micePeptidyl arginine deiminase type IVTreatment of PHUnderwent bile duct ligationSuprahepatic inferior vena cavaEndothelial cellsLower portal pressureNeutrophil chemoattractant CXCL1Intravital imagingExpression of CXCL1Inferior vena cavaRecruit neutrophilsNeutrophil recruitmentC57BL/6 miceVena cavaLess fibrinSubcutaneous injection
2016
Corrigendum to “Chronic hepatitis B: immune pathogenesis and emerging immunotherapeutics” [Curr. Opin. Pharmacol. 30 (2016) 93–105]
Chang K, Liu M. Corrigendum to “Chronic hepatitis B: immune pathogenesis and emerging immunotherapeutics” [Curr. Opin. Pharmacol. 30 (2016) 93–105]. Current Opinion In Pharmacology 2016, 30: 158-159. PMID: 27707534, DOI: 10.1016/j.coph.2016.09.005.Peer-Reviewed Original ResearchChronic hepatitis B: immune pathogenesis and emerging immunotherapeutics
Chang K, Liu M. Chronic hepatitis B: immune pathogenesis and emerging immunotherapeutics. Current Opinion In Pharmacology 2016, 30: 93-105. PMID: 27570126, DOI: 10.1016/j.coph.2016.07.013.Peer-Reviewed Original ResearchConceptsImmune modulatory approachesChronic hepatitis B.Chronic viral infectionsHost immune componentsImmune pathogenesisHBV infectionFunctional cureHepatitis BHepatitis B.Tumor immunotherapyModulatory approachesImmune componentsImmune interactionsClinical developmentViral infectionDisease pathogenesisNatural historyPathogenic responsesAspects of hostImmunotherapeuticsPathogenesisTumor therapyInfectionImmunotherapyTherapy
2014
Polyreactivity and Autoreactivity among HIV-1 Antibodies
Liu M, Yang G, Wiehe K, Nicely N, Vandergrift N, Rountree W, Bonsignori M, Alam S, Gao J, Haynes B, Kelsoe G. Polyreactivity and Autoreactivity among HIV-1 Antibodies. Journal Of Virology 2014, 89: 784-798. PMID: 25355869, PMCID: PMC4301171, DOI: 10.1128/jvi.02378-14.Peer-Reviewed Original ResearchConceptsNeutralization breadthMembrane-proximal external regionMultiple HIV-1 cladesCD4 T-cell depletionChronic antigen exposureHIV-1 AbT-cell depletionHIV-1 infectionHIV-1 vaccineHIV-1 antibodiesHIV-1 cladesHIV-1 CD4HIV-1 envelopeHIV-1 neutralizationAntigen exposureChronic inflammationHumoral responseInfected patientsProtective vaccineImmune regulationHIV-1AutoreactivityAutoreactive propertiesAg exposureHost Ag