Featured Publications
The 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 termSuper 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 treatmentHepatic 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 inflammation
2021
Endothelial 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 expression
2020
GIPC-Regulated IGFBP-3 Promotes HSC Migration In Vitro and Portal Hypertension In Vivo Through a β1-Integrin Pathway
Yaqoob U, Luo F, Greuter T, Sakrikar N, Sehrawat T, Lu J, Hu X, Gao J, Kostallari E, Chen J, Arab J, Martin-Mateos R, Cao S, Shah V. GIPC-Regulated IGFBP-3 Promotes HSC Migration In Vitro and Portal Hypertension In Vivo Through a β1-Integrin Pathway. Cellular And Molecular Gastroenterology And Hepatology 2020, 10: 545-559. PMID: 32447051, PMCID: PMC7399184, DOI: 10.1016/j.jcmgh.2020.05.005.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAdaptor Proteins, Signal TransducingAnimalsBiomarkersCell MovementCells, CulturedDisease Models, AnimalEpigenesis, GeneticGene Knockdown TechniquesHepatic Stellate CellsHistonesHumansHypertension, PortalInsulin-Like Growth Factor Binding Protein 3Integrin beta1Liver CirrhosisMiceMice, KnockoutPhosphorylationPrimary Cell CultureSignal TransductionTransforming Growth Factor betaUp-RegulationConceptsHepatic stellate cellsPortal hypertensionIGFBP-3Quantitative polymerase chain reactionWestern blot analysisLiver fibrosisPolymerase chain reactionHSC migrationChromatin immunoprecipitationChronic liver injury modelInsulin-like growth factorActivation targetGrowth factorQuiescent hepatic stellate cellsIGFBP-3 increaseTransport proteinsChronic liver diseaseChain reactionLiver injury modelIntegrin-dependent phosphorylationHistone 3 lysine 27 acetylationGene regulation changesHSC activation markersEnzyme-linked immunosorbent assayEnzyme-linked immunosorbent