2021
GIMAP5 maintains liver endothelial cell homeostasis and prevents portal hypertension
Drzewiecki K, Choi J, Brancale J, Leney-Greene MA, Sari S, Dalgiç B, Aksu A, Şahin G, Ozen A, Baris S, Karakoc-Aydiner E, Jain D, Kleiner D, Schmalz M, Radhakrishnan K, Zhang J, Hoebe K, Su HC, Pereira JP, Lenardo MJ, Lifton RP, Vilarinho S. GIMAP5 maintains liver endothelial cell homeostasis and prevents portal hypertension. Journal Of Experimental Medicine 2021, 218: e20201745. PMID: 33956074, PMCID: PMC8105721, DOI: 10.1084/jem.20201745.Peer-Reviewed Original ResearchConceptsLiver sinusoidal endothelial cellsPortal hypertensionEndothelial cell homeostasisHepatic endothelial cellsEndothelial cellsLiver diseaseUnexplained portal hypertensionGlobal health problemSinusoidal endothelial cellsCell homeostasisSingle-cell RNA-sequencing analysisHypertensionMouse modelHealth problemsMice resultsGimap5RNA sequence analysisMajor contributorCritical regulatorDiseaseCellsDamaging mutationsHomeostasisDecompensationMorbidity
2017
Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response
Cai SY, Ouyang X, Chen Y, Soroka CJ, Wang J, Mennone A, Wang Y, Mehal WZ, Jain D, Boyer JL. Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response. JCI Insight 2017, 2: e90780. PMID: 28289714, PMCID: PMC5333973, DOI: 10.1172/jci.insight.90780.Peer-Reviewed Original ResearchConceptsLiver injuryInflammatory responseBile acid-induced liver injuryCholestatic liver injuryInflammatory liver injuryProinflammatory cytokine expressionCholestatic liver diseaseBile duct ligationVivo mouse modelHepatic infiltrationInflammatory injurySerum aminotransferasesLiver diseaseCholestatic patientsCytokine expressionChemokine inductionPathophysiologic concentrationsNeutrophil chemotaxisDuct ligationPathophysiologic levelsMouse modelNew therapiesInnate immunityInjuryPeriportal areas
2016
αvβ6 Integrin Promotes Castrate-Resistant Prostate Cancer through JNK1-Mediated Activation of Androgen Receptor
Lu H, Wang T, Li J, Fedele C, Liu Q, Zhang J, Jiang Z, Jain D, Iozzo RV, Violette SM, Weinreb PH, Davis RJ, Gioeli D, FitzGerald TJ, Altieri DC, Languino LR. αvβ6 Integrin Promotes Castrate-Resistant Prostate Cancer through JNK1-Mediated Activation of Androgen Receptor. Cancer Research 2016, 76: 5163-5174. PMID: 27450452, PMCID: PMC5012867, DOI: 10.1158/0008-5472.can-16-0543.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, NeoplasmCell Line, TumorDisease Models, AnimalFlow CytometryFluorescent Antibody TechniqueGene Knockdown TechniquesHumansImmunohistochemistryIntegrinsMaleMiceMice, KnockoutMitogen-Activated Protein Kinase 8Prostatic Neoplasms, Castration-ResistantReceptors, AndrogenSignal TransductionConceptsΑvβ6 expressionAndrogen receptorProstate cancerΑvβ6 integrinCastrate-resistant prostate cancerProstate cancer mouse modelAbsence of androgenFurther clinical developmentProstate cancer therapyCancer mouse modelNormal prostatic epitheliumProstate cancer progressionΑv-containing integrinsMajor therapeutic targetUpregulation of survivinActivation of JNK1Androgen ablationDownstream kinase activationMechanisms of resistanceProstatic adenocarcinomaInvolvement of p38Preclinical resultsMouse modelProstatic epitheliumClinical development
2008
CD8+ but not CD4+ T cells require cognate interactions with target tissues to mediate GVHD across only minor H antigens, whereas both CD4+ and CD8+ T cells require direct leukemic contact to mediate GVL
Matte-Martone C, Liu J, Jain D, McNiff J, Shlomchik WD. CD8+ but not CD4+ T cells require cognate interactions with target tissues to mediate GVHD across only minor H antigens, whereas both CD4+ and CD8+ T cells require direct leukemic contact to mediate GVL. Blood 2008, 111: 3884-3892. PMID: 18223170, PMCID: PMC2275040, DOI: 10.1182/blood-2007-11-125294.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesDisease Models, AnimalGraft vs Host DiseaseGraft vs Leukemia EffectHistocompatibility Antigens Class IHistocompatibility Antigens Class IIHumansLeukemia, Myelogenous, Chronic, BCR-ABL PositiveMiceMice, KnockoutMinor Histocompatibility AntigensReceptors, Antigen, T-CellStem Cell TransplantationTransplantation ChimeraTransplantation, HomologousConceptsCD4 cellsT cellsT cell antigen receptorAllogeneic stem cell transplantationMajor histocompatibility complex class IDirect cytolytic actionDistinct effector mechanismsDonor CD4 cellsDonor T cellsStem cell transplantationHistocompatibility complex class IMinor H antigensClass II moleculesComplex class IHost diseaseBCR-ABL cDNAGVHDEffector mechanismsMouse modelCML cellsBone marrowCognate interactionNoncytolytic pathwaysCD8Cytolytic actionBiliary and Pancreatic Dysgenesis in Mice Harboring a Mutation in Pkhd1
Gallagher AR, Esquivel EL, Briere TS, Tian X, Mitobe M, Menezes LF, Markowitz GS, Jain D, Onuchic LF, Somlo S. Biliary and Pancreatic Dysgenesis in Mice Harboring a Mutation in Pkhd1. American Journal Of Pathology 2008, 172: 417-429. PMID: 18202188, PMCID: PMC2312372, DOI: 10.2353/ajpath.2008.070381.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile DuctsBiliary TractBlotting, SouthernBlotting, WesternCiliaDisease Models, AnimalHumansImmunohistochemistryIn Situ HybridizationKidney Tubules, ProximalLiver DiseasesMiceMice, Mutant StrainsMutationPancreatic DiseasesPolycystic Kidney, Autosomal RecessiveReceptors, Cell SurfaceReverse Transcriptase Polymerase Chain ReactionConceptsPolycystic kidney diseaseAutosomal recessive polycystic kidney diseaseRecessive polycystic kidney diseaseKidney diseaseMouse modelCommon bile duct dilationBile duct dilationBile duct proliferationAutosomal dominant polycystic kidney diseaseProgressive cyst formationDistal nephron segmentsDominant polycystic kidney diseaseExtrahepatic manifestationsDuct dilationBiliary tractPeriportal fibrosisDuct proliferationBile ductFibrocystic diseaseOrthologous modelPancreatic cystsProximal tubulesMice harboringSusceptibility of tissuesNephron segments
2004
Donor APCs are required for maximal GVHD but not for GVL
Matte CC, Liu J, Cormier J, Anderson BE, Athanasiadis I, Jain D, McNiff J, Shlomchik WD. Donor APCs are required for maximal GVHD but not for GVL. Nature Medicine 2004, 10: 987-992. PMID: 15286785, DOI: 10.1038/nm1089.Peer-Reviewed Original ResearchConceptsDonor antigen-presenting cellsAntigen-presenting cellsCD8 cellsMouse modelDonor major histocompatibility complex (MHC) class IBone marrowDonor-derived antigen-presenting cellsChronic phase chronic myelogenous leukemiaHematopoietic antigen-presenting cellsRecipient antigen-presenting cellsHost antigen-presenting cellsMajor histocompatibility complex class IAlloreactive CD8 cellsRecipients of MHCHistocompatibility complex class IDonor-derived cellsMinor histocompatibility antigensChronic myelogenous leukemiaDeficient bone marrowComplex class IHost diseaseGVHDHistocompatibility antigensMyelogenous leukemiaInitial priming