Featured Publications
Circulating 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 countsDiseaseDrinkersThe 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 termAn Open‐Label, Dose‐Escalation Study to Assess the Safety and Efficacy of IL‐22 Agonist F‐652 in Patients With Alcohol‐associated Hepatitis
Arab J, Sehrawat T, Simonetto D, Verma V, Feng D, Tang T, Dreyer K, Yan X, Daley W, Sanyal A, Chalasani N, Radaeva S, Yang L, Vargas H, Ibacache M, Gao B, Gores G, Malhi H, Kamath P, Shah V. An Open‐Label, Dose‐Escalation Study to Assess the Safety and Efficacy of IL‐22 Agonist F‐652 in Patients With Alcohol‐associated Hepatitis. Hepatology 2020, 72: 441-453. PMID: 31774566, PMCID: PMC7250715, DOI: 10.1002/hep.31046.Peer-Reviewed Original ResearchConceptsAlcohol-associated hepatitisSevere alcohol-associated hepatitisSerious adverse eventsMELD scoreDay 28Hepatic regenerationLille scoreAdverse eventsInterleukin-22Randomized placebo-controlled trialDose-escalating studyPlacebo-controlled trialDose-escalation studyMarkers of inflammationComparator cohortOpen labelFirst doseInflammatory markersSerum aminotransferasesSerum cytokinesEfficacy signalsSerum bilirubinMean agePatient cohortRegeneration markersLong non-coding RNA ACTA2-AS1 promotes ductular reaction by interacting with the p300/ELK1 complex
Navarro-Corcuera A, Sehrawat T, Jalan-Sakrikar N, Gibbons H, Pirius N, Khanal S, Hamdan F, Aseem S, Cao S, Banales J, Kang N, Faubion W, LaRusso N, Shah V, Huebert R. Long non-coding RNA ACTA2-AS1 promotes ductular reaction by interacting with the p300/ELK1 complex. Journal Of Hepatology 2021, 76: 921-933. PMID: 34953958, PMCID: PMC8934273, DOI: 10.1016/j.jhep.2021.12.014.Peer-Reviewed Original ResearchConceptsBile duct ligationDuctular reactionACTA2-AS1KO miceBile duct cellsLPS exposureBiliary diseaseFibrogenic markersInjury modelDuct ligationFibrogenic genesLong non-coding RNAsFl/Cholangiocyte proliferationFibrosisHuman cholangiocytesSGC-CBP30Primary cholangiocytesAbstractTextLiver tissueLAY SUMMARYP300 inhibitorTranscription factorsCholangiocytesDuct cellsMechanical 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 injectionSuper 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 treatmentXIAP Knockdown in Alcohol-Associated Liver Disease Models Exhibits Divergent in vitro and in vivo Phenotypes Owing to a Potential Zonal Inhibitory Role of SMAC
He L, Sehrawat T, Verma V, Navarro-Corcuera A, Sidhu G, Mauer A, Luo X, Katsumi T, Chen J, Shah S, Arab J, Cao S, Kashkar H, Gores G, Malhi H, Shah V. XIAP Knockdown in Alcohol-Associated Liver Disease Models Exhibits Divergent in vitro and in vivo Phenotypes Owing to a Potential Zonal Inhibitory Role of SMAC. Frontiers In Physiology 2021, 12: 664222. PMID: 34025452, PMCID: PMC8138467, DOI: 10.3389/fphys.2021.664222.Peer-Reviewed Original ResearchAlcohol-associated liver diseaseLiver diseaseTreatment of ALDAggravated liver injuryAdvanced liver diseasePrimary hepatocytesBone marrow-derived macrophagesCaspase-3Marrow-derived macrophagesMechanisms of pathogenesisHuman liver tissueInflammatory markersInflammation markersLiver injuryCCl4 modelLiver steatosisClinical trialsCommon causeAnti-apoptotic proteinsKnockout micePeriportal regionHepatocyte apoptosisLiver tissueLow expressionALD modelQuantitative assessment of portal hypertension with bi-parametric dual-frequency hepatic MR elastography in mouse models
Li J, Sehrawat T, Chen J, Hilscher M, Glaser K, Arab J, De Assuncao T, Simonetto D, Mounajjed T, Manduca A, Ehman R, Shah V, Yin M. Quantitative assessment of portal hypertension with bi-parametric dual-frequency hepatic MR elastography in mouse models. European Radiology 2020, 31: 2303-2311. PMID: 33026502, PMCID: PMC7981248, DOI: 10.1007/s00330-020-07341-3.Peer-Reviewed Original ResearchConceptsPortal hypertensionPortal pressureHepatic MR elastographyMouse modelHigh diagnostic accuracyDiagnostic accuracyHepatic fibrosisMR elastographyWild-type male miceHypertension mouse modelSignificant portal hypertensionCholestatic liver injuryCholestatic liver diseaseLiver MR elastographySham miceLiver diseaseLiver injuryHepatic congestionLiver fibrosisMale micePreclinical modelsTreatment efficacyFibrosisHypertensionDeLong testRegulation 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 proteinsPost-acute COVID-19 syndrome
Nalbandian A, Sehgal K, Gupta A, Madhavan M, McGroder C, Stevens J, Cook J, Nordvig A, Shalev D, Sehrawat T, Ahluwalia N, Bikdeli B, Dietz D, Der-Nigoghossian C, Liyanage-Don N, Rosner G, Bernstein E, Mohan S, Beckley A, Seres D, Choueiri T, Uriel N, Ausiello J, Accili D, Freedberg D, Baldwin M, Schwartz A, Brodie D, Garcia C, Elkind M, Connors J, Bilezikian J, Landry D, Wan E. Post-acute COVID-19 syndrome. Nature Medicine 2021, 27: 601-615. PMID: 33753937, PMCID: PMC8893149, DOI: 10.1038/s41591-021-01283-z.Peer-Reviewed Original ResearchConceptsPost-acute COVID-19COVID-19Post-acute COVID-19 syndromeSevere acute respiratory syndrome coronavirus 2Dedicated COVID-19 clinicsAcute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Organ-specific sequelaeAcute COVID-19Long-term complicationsMulti-organ diseaseOnset of symptomsPopulation of patientsCOVID-19 syndromeCOVID-19 survivorsCoronavirus disease 2019 (COVID-19) pandemicCOVID-19 clinicSyndrome coronavirus 2Disease 2019 pandemicPatient advocacy groupsGlobal healthcare crisisViral syndromePersistent symptomsMultidisciplinary careCoronavirus 2Extrapulmonary manifestations of COVID-19
Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, Bikdeli B, Ahluwalia N, Ausiello JC, Wan EY, Freedberg DE, Kirtane AJ, Parikh SA, Maurer MS, Nordvig AS, Accili D, Bathon JM, Mohan S, Bauer KA, Leon MB, Krumholz HM, Uriel N, Mehra MR, Elkind MSV, Stone GW, Schwartz A, Ho DD, Bilezikian JP, Landry DW. Extrapulmonary manifestations of COVID-19. Nature Medicine 2020, 26: 1017-1032. PMID: 32651579, DOI: 10.1038/s41591-020-0968-3.Peer-Reviewed Original ResearchConceptsExtrapulmonary manifestationsCOVID-19Acute kidney injuryAcute coronary syndromeSpectrum of manifestationsCoronavirus SARS-CoV-2SARS-CoV-2Coronary syndromeGastrointestinal symptomsKidney injuryOcular symptomsThrombotic complicationsHepatocellular injuryEndothelial damageMyocardial dysfunctionDermatologic complicationsNeurologic illnessRespiratory pathologyImmune responseExtrapulmonary tissuesTherapeutic strategiesEntry receptorTissue damageOrgan systemsInjuryEpigenetics of alcohol-related liver diseases
Habash N, Sehrawat T, Shah V, Cao S. Epigenetics of alcohol-related liver diseases. JHEP Reports 2022, 4: 100466. PMID: 35462859, PMCID: PMC9018389, DOI: 10.1016/j.jhepr.2022.100466.Peer-Reviewed Original ResearchAlcohol-related liver diseaseLiver diseaseMajor public health problemChronic liver diseasePublic health problemProinflammatory roleSignificant morbidityMultiple disease statesHealth problemsDisease statesDiseaseClinical applicationNon-coding RNADiagnosisEpigenetic alterationsPrimary causeCurrent knowledgeEpigenetic changesReview articleStudy of epigeneticsHepatologistsMorbidityComplicationsChemokinesPathophysiologyAlcohol-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 ResearchHepatic stellate cell activation promotes alcohol-induced steatohepatitis through Igfbp3 and SerpinA12
Arab J, Cabrera D, Sehrawat T, Jalan-Sakrikar N, Verma V, Simonetto D, Cao S, Yaqoob U, Leon J, Freire M, Vargas J, De Assuncao T, Kwon J, Guo Y, Kostallari E, Cai Q, Kisseleva T, Oh Y, Arrese M, Huebert R, Shah V. Hepatic stellate cell activation promotes alcohol-induced steatohepatitis through Igfbp3 and SerpinA12. Journal Of Hepatology 2020, 73: 149-160. PMID: 32087348, PMCID: PMC7305991, DOI: 10.1016/j.jhep.2020.02.005.Peer-Reviewed Original ResearchConceptsHepatic stellate cellsAlcohol-induced steatohepatitisNeuropilin-1HSC activationStellate cellsWild-type HSCsLower hepatic triglyceride contentAlcohol-related liver diseaseHepatic stellate cell activationMarkers of steatosisNRP-1 knockdownParenchymal cell injuryDevelopment of steatohepatitisHepatic triglyceride contentEthanol-induced steatosisStellate cell activationAlcoholic hepatitisLipid droplet formationAlcohol feedingLiver diseaseAlcohol damageLess fibrosisLiver fibrosisRegulation of IGFBP3Less inflammationUtility and Limitations of Glycated Hemoglobin (HbA1c) in Patients with Liver Cirrhosis as Compared with Oral Glucose Tolerance Test for Diagnosis of Diabetes
Sehrawat T, Jindal A, Kohli P, Thour A, Kaur J, Sachdev A, Gupta Y. Utility and Limitations of Glycated Hemoglobin (HbA1c) in Patients with Liver Cirrhosis as Compared with Oral Glucose Tolerance Test for Diagnosis of Diabetes. Diabetes Therapy 2018, 9: 243-251. PMID: 29305791, PMCID: PMC5801248, DOI: 10.1007/s13300-017-0362-4.Peer-Reviewed Original ResearchOral glucose tolerance testDiagnosis of diabetesSeverity of cirrhosisGlucose tolerance testWorld Health OrganizationLiver cirrhosisSevere anemiaTolerance testStandard oral glucose tolerance testCTP class AGold-standard oral glucose tolerance testPrevalence of diabetesEffect of anemiaSeverity of anemiaNegative predictive valuePugh scoreChild-TurcotteOGTT resultsPatient departmentHospitalized patientsOGTT criteriaWHO criteriaResultsA totalGlycated hemoglobinCirrhosis
2024
Portal Fibrosis and the Ductular Reaction: Pathophysiological Role in the Progression of Liver Disease and Translational Opportunities
Gupta V, Sehrawat T, Pinzani M, Strazzabosco M. Portal Fibrosis and the Ductular Reaction: Pathophysiological Role in the Progression of Liver Disease and Translational Opportunities. Gastroenterology 2024 PMID: 39251168, DOI: 10.1053/j.gastro.2024.07.044.Peer-Reviewed Original ResearchLiver diseasePortal fibrosisDuctular reactionPathological repairProgression of liver diseaseCholestatic liver diseaseTranslational opportunitiesChronic liver diseaseProgression of fibrosisCell typesChronic human liver diseaseHuman liver diseaseTumor microenvironmentTherapeutic advancesImmune modulationHistological abnormalitiesVascular changesLiver repairPathophysiological roleFibrosisTreatment prospectsPortal spacesMesenchymal cellsVascular cellsComplex crosstalkLiver Sinusoidal Endothelial Cells Contribute to Portal Hypertension Through Collagen Type IV–Driven Sinusoidal Remodeling
Gan C, Yaqoob U, Lu J, Xie M, Anwar A, Jalan-Sakrikar N, Jerez S, Sehrawat T, Navarro-Corcuera A, Kostallari E, Habash N, Cao S, Shah V. Liver Sinusoidal Endothelial Cells Contribute to Portal Hypertension Through Collagen Type IV–Driven Sinusoidal Remodeling. JCI Insight 2024, 9: e174775. PMID: 38713515, PMCID: PMC11382879, DOI: 10.1172/jci.insight.174775.Peer-Reviewed Original ResearchLiver sinusoidal endothelial cellsPortal hypertensionSinusoidal remodelingSinusoidal endothelial cellsSinusoidal resistanceComplication of liver cirrhosisEndothelial cellsSinusoidal endothelial cells in vitroEnhancer-promoter interactionsEpigenome editing approachesEndothelial cells in vitroChronic liver injuryCells in vitroMouse fibrotic liversCollagen type IVLiver cirrhosisGene mutationsExpression regulationLiver fibrosisLiver injuryEpigenetic repressionLiver diseaseCellular sourceCol4 expressionImmunofluorescence stainingA Pilot Study on the Proteomics Profile of Serum Exosome-Enriched Extracellular Vesicles from Normal versus Individuals with Obesity-Related Insulin Resistance
Saraswathi V, Ai W, Kumar V, Sharma K, Gopal T, Kumar N, Malhi H, Sehrawat T, Desouza C. A Pilot Study on the Proteomics Profile of Serum Exosome-Enriched Extracellular Vesicles from Normal versus Individuals with Obesity-Related Insulin Resistance. Biomedicines 2024, 12: 799. PMID: 38672154, PMCID: PMC11048419, DOI: 10.3390/biomedicines12040799.Peer-Reviewed Original ResearchObesity-related insulin resistanceIngenuity Pathway AnalysisInsulin resistanceB cellsRegulate immune cell activationSerum exosomesImmune cell activationIsolated serum exosomesB cell activationRisk of diabetesHigh-risk individualsExosome-enriched extracellular vesiclesProteomic profilingProgression of diabetesIngenuity Pathway Analysis analysesCell activationInsulin sensitivityProtein expressionOB-IRExosomal proteinsTherapeutic targetMale subjectsExtracellular vesiclesExtracellular spaceInflammation
2023
Modulating sphingosine 1-phosphate receptor signaling skews intrahepatic leukocytes and attenuates murine nonalcoholic steatohepatitis
Liao C, Barrow F, Venkatesan N, Nakao Y, Mauer A, Fredrickson G, Song M, Sehrawat T, Dasgupta D, Graham R, Revelo X, Malhi H. Modulating sphingosine 1-phosphate receptor signaling skews intrahepatic leukocytes and attenuates murine nonalcoholic steatohepatitis. Frontiers In Immunology 2023, 14: 1130184. PMID: 37153573, PMCID: PMC10160388, DOI: 10.3389/fimmu.2023.1130184.Peer-Reviewed Original ResearchConceptsMurine nonalcoholic steatohepatitisNonalcoholic steatohepatitisLiver injuryHepatic macrophage accumulationT cellsIntrahepatic leukocytesDietary feedingNKT cellsMacrophage accumulationReceptor antagonismLeukocyte populationsB cellsDouble-negative T cellsReceptor-specific modulationNegative T cellsStandard chow dietImmune cell populationsC57BL/6 male miceCirculating MarkersLiver histologyProinflammatory markersNK cellsOral gavageChow dietNASH progressionLoss of CEACAM1 in endothelial cells causes hepatic fibrosis
Muturi H, Ghadieh H, Abdolahipour R, Stankus H, Belew G, Liu J, Jahromi M, Lee A, Singer B, Angeli-Pahim I, Sehrawat T, Malhi H, Verhulst S, van Grunsven L, Zarrinpar A, Duarte S, Najjar S. Loss of CEACAM1 in endothelial cells causes hepatic fibrosis. Metabolism 2023, 144: 155562. PMID: 37088122, PMCID: PMC10330196, DOI: 10.1016/j.metabol.2023.155562.Peer-Reviewed Original ResearchConceptsFl/Hepatic fibrosisEndothelial lossVisceral obesityImmunohistochemical analysisWild-type HSCsEndothelial cellsHepatic fibrosis stageLiver tissue biopsiesHepatic stellate cellsNF-κB signalingLiver endothelial cellsNF-κB targetsLiver transplantAdult patientsBariatric surgerySystemic inflammationInflammatory infiltrationLiver biopsyNASH pathogenesisInsulin resistanceFibrosis stageInsulin sensitivityHepatic fibrogenesisMale mice