Featured Publications
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 treatmentRegulation 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 proteins
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
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