2023
IL-6 trans-signaling in a humanized mouse model of scleroderma
Odell I, Agrawal K, Sefik E, Odell A, Caves E, Kirkiles-Smith N, Horsley V, Hinchcliff M, Pober J, Kluger Y, Flavell R. IL-6 trans-signaling in a humanized mouse model of scleroderma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2306965120. PMID: 37669366, PMCID: PMC10500188, DOI: 10.1073/pnas.2306965120.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBasidiomycotaDisease Models, AnimalEndothelial CellsHumansInterleukin-6MiceScleroderma, LocalizedSkinConceptsBone marrow-derived immune cellsIL-6Human hematopoietic stem cellsImmune cellsT cellsScleroderma skinSoluble IL-6 receptorCD8 T cellsHumanized mouse modelPathogenesis of sclerodermaMesenchymal cellsFibroblast-derived IL-6IL-6 receptorIL-6 signalingT cell activationHuman IL-6Human T cellsExpression of collagenFibrosis improvementPansclerotic morpheaHuman endothelial cellsHumanized miceReduced markersSkin graftsHuman CD4Transendothelial Migration of Human B Cells: Chemokine versus Antigen.
Wang V, Pober J, Manes T. Transendothelial Migration of Human B Cells: Chemokine versus Antigen. The Journal Of Immunology 2023, 211: 923-931. PMID: 37530585, PMCID: PMC10529164, DOI: 10.4049/jimmunol.2200887.Peer-Reviewed Original ResearchConceptsB cellsLeukocyte cell adhesion moleculeTransendothelial migrationEndothelial cellsCell adhesion moleculeAdhesion moleculesPeripheral blood CD19B cell subsetsMemory B cellsInnate immune propertiesSites of inflammationMicrovascular endothelial cellsHuman microvascular endothelial cellsHuman B cellsBlood CD19Peripheral bloodCell subsetsVenular flowT cellsICAM-1VCAM-1Immune propertiesSyk activationChemokinesExpression of genesA ZFYVE21-Rubicon-RNF34 signaling complex promotes endosome-associated inflammasome activity in endothelial cells
Li X, Jiang Q, Song G, Barkestani M, Wang Q, Wang S, Fan M, Fang C, Jiang B, Johnson J, Geirsson A, Tellides G, Pober J, Jane-wit D. A ZFYVE21-Rubicon-RNF34 signaling complex promotes endosome-associated inflammasome activity in endothelial cells. Nature Communications 2023, 14: 3002. PMID: 37225719, PMCID: PMC10209169, DOI: 10.1038/s41467-023-38684-2.Peer-Reviewed Original ResearchConceptsEndothelial cellsInflammasome activityMembrane attack complexCaspase-1Potential therapeutic targetChronic rejectionComplement membrane attack complexTissue inflammationNLRP3 inflammasomeTissue injuryMouse modelTherapeutic targetDependent mannerInflammationAttack complexInflammasomeHuman tissuesFlightless IInhibitory associationsSkin modelRNF34CellsSingle-cell atlas of the human neonatal small intestine affected by necrotizing enterocolitis
Egozi A, Olaloye O, Werner L, Silva T, McCourt B, Pierce R, An X, Wang F, Chen K, Pober J, Shouval D, Itzkovitz S, Konnikova L. Single-cell atlas of the human neonatal small intestine affected by necrotizing enterocolitis. PLOS Biology 2023, 21: e3002124. PMID: 37205711, PMCID: PMC10234541, DOI: 10.1371/journal.pbio.3002124.Peer-Reviewed Original ResearchMeSH KeywordsEndothelial CellsEnterocolitis, NecrotizingHumansInfantInfant, NewbornInfant, PrematureIntestinal MucosaIntestine, SmallIntestinesConceptsSingle-cell RNA sequencingSingle-cell atlasEpithelial cellsCell identityRNA sequencingBulk transcriptomicsCellular dysregulationAberrant interactionsNeonatal small intestinePotential targetCellular changesBiomarker discoveryGastrointestinal complicationsPremature infantsProinflammatory macrophagesProinflammatory genesClonal expansionT cellsEndothelial cellsImmune interactionsIntestinal tissueCellsSmall intestineComprehensive viewNECIntegrated Analysis of Tracheobronchial Fluid from Before and After Cardiopulmonary Bypass Reveals Activation of the Integrated Stress Response and Altered Pulmonary Microvascular Permeability
Habet V, Li N, Qi J, Peng G, Charkoftaki G, Vasiliou V, Sharma L, Pober J, Dela Cruz C, Yan X, Pierce R. Integrated Analysis of Tracheobronchial Fluid from Before and After Cardiopulmonary Bypass Reveals Activation of the Integrated Stress Response and Altered Pulmonary Microvascular Permeability. The Yale Journal Of Biology And Medicine 2023, 96: 23-42. PMID: 37009190, PMCID: PMC10052603, DOI: 10.59249/kfyz8002.Peer-Reviewed Original ResearchMeSH KeywordsCapillary PermeabilityCardiopulmonary BypassChildChild, PreschoolEndothelial CellsHumansLungProteomicsConceptsIntegrated stress responseProteomic analysisTranscriptional activityStress responseSingle-cell RNA sequencingCell RNA sequencingHuman pulmonary microvascular endothelial cellsMulti-omics approachCell type annotationRespiratory transport chainUnbiased proteomic analysisUpregulation of proteinsIngenuity Pathway AnalysisCardiopulmonary bypassCell clusteringProtective cellular responseFunctional cellular assaysDistinct cell populationsDEG analysisCellular phenotypesRNA sequencingPathway analysisTransport chainCellular responsesImmune cellsHedgehog-induced ZFYVE21 promotes chronic vascular inflammation by activating NLRP3 inflammasomes in T cells
Jiang B, Wang S, Song G, Jiang Q, Fan M, Fang C, Li X, Soh C, Manes T, Cheru N, Qin L, Ren P, Jortner B, Wang Q, Quaranta E, Yoo P, Geirsson A, Davis R, Tellides G, Pober J, Jane-Wit D. Hedgehog-induced ZFYVE21 promotes chronic vascular inflammation by activating NLRP3 inflammasomes in T cells. Science Signaling 2023, 16: eabo3406. PMID: 36943921, PMCID: PMC10061549, DOI: 10.1126/scisignal.abo3406.Peer-Reviewed Original ResearchConceptsIschemia-reperfusion injuryChronic vascular inflammationT cellsNLRP3 inflammasomeVascular inflammationChronic inflammationEndothelial cellsIFN-γ responsesControl T cellsNLRP3 inflammasome activityT memory cellsAllograft vasculopathyVascular sequelaeHuman endothelial cellsCoronary arteryEffector responsesCell-autonomous roleInflammasome activityMouse modelInflammationPatient samplesVigorous recruitmentInflammasomePrimary human cellsImmune signaling
2022
Monobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications
Albert C, Bracaglia L, Koide A, DiRito J, Lysyy T, Harkins L, Edwards C, Richfield O, Grundler J, Zhou K, Denbaum E, Ketavarapu G, Hattori T, Perincheri S, Langford J, Feizi A, Haakinson D, Hosgood SA, Nicholson ML, Pober JS, Saltzman WM, Koide S, Tietjen GT. Monobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications. Nature Communications 2022, 13: 5998. PMID: 36220817, PMCID: PMC9553936, DOI: 10.1038/s41467-022-33490-8.Peer-Reviewed Original ResearchMeSH KeywordsAminesAntibodiesDrug Delivery SystemsEndothelial CellsHumansNanomedicineNanoparticlesOligonucleotidesConceptsTargeted delivery applicationsTargeted nanoparticlesAntibody immobilizationAntigen-binding functionNanoparticlesNP surfaceDelivery applicationsRobust deliveryEndothelial cellsAmine couplingAntibody displayClinical translationIntracellular drug levelsVascular endothelial cellsCultured endothelial cellsNanomedicineDrug levelsVivo perfusionOrgan transplantsAdapterClinical settingHuman kidneyHuman settingImmobilizationEfficacyCostimulators expressed on human endothelial cells modulate antigen-dependent recruitment of circulating T lymphocytes
Manes TD, Wang V, Pober JS. Costimulators expressed on human endothelial cells modulate antigen-dependent recruitment of circulating T lymphocytes. Frontiers In Immunology 2022, 13: 1016361. PMID: 36275645, PMCID: PMC9582530, DOI: 10.3389/fimmu.2022.1016361.Peer-Reviewed Original ResearchMeSH KeywordsCD28 AntigensCD58 AntigensEndothelial CellsHumansImmunologic MemoryInterleukin-2Receptors, Antigen, T-CellSuperantigensConceptsT effector cellsT cellsTransendothelial migrationEndothelial cellsCheckpoint inhibitorsEffector cellsCytokine productionCytokine synthesisPeripheral blood T cell subpopulationsEffector memory T cellsEngagement of OX40Presentation of superantigensRegulatory T cellsMemory T cellsT cell subpopulationsT-cell typeT cell CD28Antigen-independent signalT cell activationT cell receptorHuman dermal microvascularCD8 effectorsT-regsHuman endothelial cellsActivated CD4Wanted: An endothelial cell targeting atlas for nanotherapeutic delivery in allograft organs
Liburd ST, Shi AA, Pober JS, Tietjen GT. Wanted: An endothelial cell targeting atlas for nanotherapeutic delivery in allograft organs. American Journal Of Transplantation 2022, 22: 1754-1759. PMID: 35373446, PMCID: PMC9651180, DOI: 10.1111/ajt.17050.Peer-Reviewed Original ResearchConceptsNormothermic machine perfusionEndothelial cellsGraft vasculaturePoor outcomePreservation injuryMachine perfusionProfound shortageOrgan assessmentTransplant therapeuticsDonor comorbiditiesAllograft organClinical useOrgansAttractive targetNanotherapeutic deliveryTherapeutic vehiclesCellsTherapeutic deliveryDeliveryComorbiditiesTransplantGraftInjuryPerfusionVasculatureCo-Expression and Functional Interactions of Death Receptor 3 and E-Selectin in Clear Cell Renal Cell Carcinoma
Al-Lamki RS, Wang J, Pober JS, Bradley JR. Co-Expression and Functional Interactions of Death Receptor 3 and E-Selectin in Clear Cell Renal Cell Carcinoma. American Journal Of Pathology 2022, 192: 722-736. PMID: 35063404, DOI: 10.1016/j.ajpath.2021.12.010.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinaseCell cycle entryCcRCC cellsDeath receptor 3Protein kinaseClear cell renal cell carcinoma cellsProximity ligation assayRenal cell carcinoma cellsReceptor 3E-selectinPotential new targetsCycle entryNF-κB-dependent mannerNF-κBLigation assayTumor gradeCcRCC tissuesFunctional interactionSelectin expressionFunctional roleClear cell renal cell carcinomaOrgan cultureCell renal cell carcinomaExpression increasesAddition of TL1A
2021
Mitochondrial fission in allograft endothelial cells: A novel actionable target
Mullan CW, Pober JS. Mitochondrial fission in allograft endothelial cells: A novel actionable target. American Journal Of Transplantation 2021, 22: 337-338. PMID: 34865296, DOI: 10.1111/ajt.16911.Commentaries, Editorials and LettersCardiac allograft vasculopathy: current review and future research directions
Pober JS, Chih S, Kobashigawa J, Madsen JC, Tellides G. Cardiac allograft vasculopathy: current review and future research directions. Cardiovascular Research 2021, 117: 2624-2638. PMID: 34343276, PMCID: PMC8783389, DOI: 10.1093/cvr/cvab259.Peer-Reviewed Original ResearchConceptsCardiac allograft vasculopathyAllograft vasculopathyImmune-mediated vasculopathyLate graft lossGraft lossCardiac transplantationOrgan graftsTransplanted heartsCurrent therapiesVascular remodellingVasculopathyMajor causeCurrent reviewRemodellingTransplantationPathogenesisGraftTherapyPerfusionIncidenceDiagnosisVasculatureComplement‐activated human endothelial cells stimulate increased polyfunctionality in alloreactive T cells
Xie CB, Zhou J, Mackay S, Pober JS. Complement‐activated human endothelial cells stimulate increased polyfunctionality in alloreactive T cells. American Journal Of Transplantation 2021, 21: 1902-1909. PMID: 33415805, PMCID: PMC8096653, DOI: 10.1111/ajt.16485.Peer-Reviewed Original Research
2020
Mural Cell-Specific Deletion of Cerebral Cavernous Malformation 3 in the Brain Induces Cerebral Cavernous Malformations
Wang K, Zhang H, He Y, Jiang Q, Tanaka Y, Park IH, Pober JS, Min W, Zhou HJ. Mural Cell-Specific Deletion of Cerebral Cavernous Malformation 3 in the Brain Induces Cerebral Cavernous Malformations. Arteriosclerosis Thrombosis And Vascular Biology 2020, 40: 2171-2186. PMID: 32640906, DOI: 10.1161/atvbaha.120.314586.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsBrainCell CommunicationCell MovementCells, CulturedCoculture TechniquesEndothelial CellsFemaleFocal AdhesionsGene DeletionGenetic Predisposition to DiseaseHemangioma, Cavernous, Central Nervous SystemHumansMaleMembrane ProteinsMice, KnockoutMicrovesselsMyocytes, Smooth MusclePaxillinPericytesPhenotypeProtein StabilityProto-Oncogene ProteinsSignal TransductionConceptsCerebral cavernous malformationsBrain mural cellsCCM lesionsMural cellsCavernous malformationsSevere brain hemorrhageCCM pathogenesisSmooth muscle cellsWeeks of ageCell-specific deletionMural cell coverageBrain pericytesBrain hemorrhageNeonatal stageBrain vasculatureLesionsEntire brainMuscle cellsCerebral cavernous malformation 3Endothelial cellsMicePericytesSpecific deletionAdhesion formationPathogenesisAn endothelial microRNA-1–regulated network controls eosinophil trafficking in asthma and chronic rhinosinusitis
Korde A, Ahangari F, Haslip M, Zhang X, Liu Q, Cohn L, Gomez JL, Chupp G, Pober JS, Gonzalez A, Takyar SS. An endothelial microRNA-1–regulated network controls eosinophil trafficking in asthma and chronic rhinosinusitis. Journal Of Allergy And Clinical Immunology 2020, 145: 550-562. PMID: 32035607, PMCID: PMC8440091, DOI: 10.1016/j.jaci.2019.10.031.Peer-Reviewed Original ResearchConceptsMiR-1 levelsAllergic airway inflammationChronic rhinosinusitisP-selectin levelsEndothelium-specific overexpressionLung endotheliumAirway eosinophiliaAirway inflammationAsthmatic patientsTissue eosinophiliaMiR-1House dust mite modelEndothelial cellsThymic stromal lymphopoietinNumber of hospitalizationsHuman lung endotheliumIL-13 stimulationCRS cohortQuantitative RT-PCRSputum eosinophiliaAirway obstructionAsthma modelAsthma phenotypesLentiviral vector deliveryMurine model
2019
Three Dimensional Bioprinting of a Vascularized and Perfusable Skin Graft Using Human Keratinocytes, Fibroblasts, Pericytes, and Endothelial Cells
Baltazar T, Merola J, Catarino C, Xie C, Kirkiles-Smith N, Lee V, Hotta S, Dai G, Xu X, Ferreira FC, Saltzman WM, Pober JS, Karande P. Three Dimensional Bioprinting of a Vascularized and Perfusable Skin Graft Using Human Keratinocytes, Fibroblasts, Pericytes, and Endothelial Cells. Tissue Engineering Part A 2019, 26: 227-238. PMID: 31672103, PMCID: PMC7476394, DOI: 10.1089/ten.tea.2019.0201.Peer-Reviewed Original ResearchConceptsSkin graftsHuman endothelial colony-forming cellsEndothelial cellsHuman endothelial cellsHuman skin graftsEndothelial colony-forming cellsPlacental pericytesGraft survivalCutaneous ulcersAllogeneic cellsHuman foreskin keratinocytesMouse microvesselsImmunodeficient miceHuman pericytesGraftColony-forming cellsVascular structuresWound bedForeskin keratinocytesEpidermal maturationPericytesHuman placental pericytesHuman keratinocytesKeratinocytesType I
2015
Tissue-Engineered Microvasculature to Reperfuse Isolated Renal Glomeruli
Chang WG, Fornoni A, Tietjen G, Mendez JJ, Niklason LE, Saltzman WM, Pober JS. Tissue-Engineered Microvasculature to Reperfuse Isolated Renal Glomeruli. Tissue Engineering Part A 2015, 21: 2673-2679. PMID: 26414101, PMCID: PMC4652181, DOI: 10.1089/ten.tea.2015.0060.Peer-Reviewed Original Research
2014
Rapamycin antagonizes TNF induction of VCAM-1 on endothelial cells by inhibiting mTORC2
Wang C, Qin L, Manes TD, Kirkiles-Smith NC, Tellides G, Pober JS. Rapamycin antagonizes TNF induction of VCAM-1 on endothelial cells by inhibiting mTORC2. Journal Of Experimental Medicine 2014, 211: 395-404. PMID: 24516119, PMCID: PMC3949571, DOI: 10.1084/jem.20131125.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceBlotting, WesternCell AdhesionChromatin ImmunoprecipitationDNA PrimersEndothelial CellsFlow CytometryHumansImmunoblottingMechanistic Target of Rapamycin Complex 2Microscopy, FluorescenceMultiprotein ComplexesOncogene Protein v-aktReal-Time Polymerase Chain ReactionSirolimusT-LymphocytesTOR Serine-Threonine KinasesTumor Necrosis Factor-alphaVascular Cell Adhesion Molecule-1ConceptsVascular cell adhesion molecule-1VCAM-1 expressionEndothelial cellsActivation of ERK1/2Cell adhesion molecule-1TNF inductionInfiltration of leukocytesAdhesion molecule-1Inhibition of TNFPotential therapeutic targetAbility of rapamycinAbility of TNFTranscription factor IRF-1Hyperactivation of ERK1/2Inhibition of ERK1/2Venular flowT cellsEndothelial expressionInflamed tissuesVascular endotheliumMolecule-1Therapeutic targetRapamycin pretreatmentRenal glomeruliTNF
2013
Alloantibody and Complement Promote T Cell–Mediated Cardiac Allograft Vasculopathy Through Noncanonical Nuclear Factor-&kgr;B Signaling in Endothelial Cells
Jane-wit D, Manes TD, Yi T, Qin L, Clark P, Kirkiles-Smith NC, Abrahimi P, Devalliere J, Moeckel G, Kulkarni S, Tellides G, Pober JS. Alloantibody and Complement Promote T Cell–Mediated Cardiac Allograft Vasculopathy Through Noncanonical Nuclear Factor-&kgr;B Signaling in Endothelial Cells. Circulation 2013, 128: 2504-2516. PMID: 24045046, PMCID: PMC3885874, DOI: 10.1161/circulationaha.113.002972.Peer-Reviewed Original ResearchConceptsCardiac allograft vasculopathyPanel reactive antibodyNuclear factor-κB signalingFactor-κB signalingAllograft vasculopathyT cellsEndothelial cellsMembrane attack complexAlloreactive T cell activationChronic antibody-mediated rejectionNoncanonical nuclear factorProinflammatory gene programAntibody-mediated rejectionDonor-specific antibodiesGraft endothelial cellsLate allograft lossAlloreactive T cellsAllogeneic endothelial cellsT cell activationAttack complexHuman T cellsAllograft lossHeart transplantationTransplantation patientsLesion pathogenesisParacrine exchanges of molecular signals between alginate-encapsulated pericytes and freely suspended endothelial cells within a 3D protein gel
Andrejecsk JW, Cui J, Chang WG, Devalliere J, Pober JS, Saltzman WM. Paracrine exchanges of molecular signals between alginate-encapsulated pericytes and freely suspended endothelial cells within a 3D protein gel. Biomaterials 2013, 34: 8899-8908. PMID: 23973174, PMCID: PMC3839675, DOI: 10.1016/j.biomaterials.2013.08.008.Peer-Reviewed Original ResearchConceptsHuman umbilical vein endothelial cellsParacrine signalsFunctioning of tissuesProper survivalEndothelial cellsUmbilical vein endothelial cellsMolecular signalsRegulated deliveryVein endothelial cellsVessel-like structuresLiving cellsProtein gelsHepatocyte growth factorTherapeutic proteinsParacrine exchangesGrowth factorMicrovascular pericytesProteinAngiogenic proteinsCellsVascular tissue engineeringHUVEC behaviorTissue constructsPericytesLocal environment