2024
SRF SUMOylation modulates smooth muscle phenotypic switch and vascular remodeling
Xu Y, Zhang H, Chen Y, Pober J, Zhou M, Zhou J, Min W. SRF SUMOylation modulates smooth muscle phenotypic switch and vascular remodeling. Nature Communications 2024, 15: 6919. PMID: 39134547, PMCID: PMC11319592, DOI: 10.1038/s41467-024-51350-5.Peer-Reviewed Original ResearchConceptsVascular smooth muscle cellsSerum response factorCardiovascular diseaseVSMC synthetic phenotypeVascular remodelingNeointimal formationSENP1 deficiencySerum response factor activitySmooth muscle phenotypic switchingPhenotypic switchingPathogenesis of cardiovascular diseaseSmooth muscle cellsPost-translational SUMOylationTreatment of cardiovascular diseasesInhibitor AZD6244Phospho-ELK1Increased nuclear accumulationLysosomal localizationGene transcriptionNuclear accumulationMuscle cellsCoronary arteryCVD patientsVSMC phenotypic switchTherapeutic potentialEnhancing in vivo cell and tissue targeting by modulation of polymer nanoparticles and macrophage decoys
Piotrowski-Daspit A, Bracaglia L, Eaton D, Richfield O, Binns T, Albert C, Gould J, Mortlock R, Egan M, Pober J, Saltzman W. Enhancing in vivo cell and tissue targeting by modulation of polymer nanoparticles and macrophage decoys. Nature Communications 2024, 15: 4247. PMID: 38762483, PMCID: PMC11102454, DOI: 10.1038/s41467-024-48442-7.Peer-Reviewed Original ResearchConceptsPoly(amine-co-esterPolymer nanoparticlesDelivery of nucleic acid therapeuticsCell-type tropismTissue tropismNucleic acid delivery vehiclesIn vivo deliveryIn vivo efficacyCirculation half-lifeNucleic acid therapeuticsVehicle characteristicsTunable propertiesBiodistribution assessmentPhysiological fatePolymer chemistrySurface propertiesPharmacokinetic modelTissue targetingNanoparticlesDistribution modifiersPolymeric nanoparticlesTropismPolymerDelivery vehiclesHalf-life
2023
Hedgehog costimulation during ischemia-reperfusion injury potentiates cytokine and homing responses of CD4+ T cells
Wang S, Song G, Barkestani M, Tobiasova Z, Wang Q, Jiang Q, Lopez R, Adelekan-Kamara Y, Fan M, Pober J, Tellides G, Jane-wit D. Hedgehog costimulation during ischemia-reperfusion injury potentiates cytokine and homing responses of CD4+ T cells. Frontiers In Immunology 2023, 14: 1248027. PMID: 37915586, PMCID: PMC10616247, DOI: 10.3389/fimmu.2023.1248027.Peer-Reviewed Original ResearchConceptsIschemia-reperfusion injuryHuman skin xenograftsSkin xenograftsT cellsPolyfunctional cytokine responsesSolid organ transplantationT cell subsetsResponse of CD4Expression of ICOST cell populationsHumanized mouse modelPeripheral helper cellsAllograft lossIL-21PD-1Reperfusion injuryCytokine responsesVascular inflammationPolyclonal expansionHelper cellsOrgan transplantationMouse modelClinical problemCostimulatory signalsDistinct subsetsMicroRNA-1 protects the endothelium in acute lung injury
Korde A, Haslip M, Pednekar P, Khan A, Chioccioli M, Mehta S, Lopez-Giraldez F, Bermejo S, Rojas M, Dela Cruz C, Matthay M, Pober J, Pierce R, Takyar S. MicroRNA-1 protects the endothelium in acute lung injury. JCI Insight 2023, 8: e164816. PMID: 37737266, PMCID: PMC10561733, DOI: 10.1172/jci.insight.164816.Peer-Reviewed Original ResearchConceptsAcute respiratory distress syndromeAcute lung injuryVascular endothelial growth factorAngiopoietin-2Lung injuryAcute injuryMiR-1MicroRNA-1Endothelial cell-specific overexpressionSevere endothelial dysfunctionRespiratory distress syndromeSurvival of miceIntrinsic protective effectContext of injuryCell-specific overexpressionEndothelial growth factorFamily member 3Pneumonia cohortMiR-1 targetsEndothelial dysfunctionDistress syndromeBarrier dysfunctionCapillary leakProtective effectSevere formIL-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 ResearchConceptsBone 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 CD4A 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 modelRNF34CellsHedgehog-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 signalingMetabolic reprogramming by immune-responsive gene 1 up-regulation improves donor heart preservation and function
Lei I, Huang W, Noly P, Naik S, Ghali M, Liu L, Pagani F, Abou El Ela A, Pober J, Pitt B, Platt J, Cascalho M, Wang Z, Chen Y, Mortensen R, Tang P. Metabolic reprogramming by immune-responsive gene 1 up-regulation improves donor heart preservation and function. Science Translational Medicine 2023, 15: eade3782. PMID: 36753565, PMCID: PMC10068866, DOI: 10.1126/scitranslmed.ade3782.Peer-Reviewed Original ResearchConceptsImmune response gene 1Primary graft dysfunctionDonor heart preservationValproic acidDonor heartsVPA treatmentHeart preservationHeart functionImmune-responsive gene 1Donor heart functionHistone deacetylase inhibitor valproic acidImproved heart functionAntioxidant protein expressionMetabolic reprogrammingDonor-recipient matchingPromising therapeutic strategyHuman donor heartsInhibitor valproic acidGene 1Graft dysfunctionCardioprotective effectsKetoglutarate solutionTherapeutic strategiesResponse gene-1Nuclear factor
2022
Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes
Perdigoto AL, Deng S, Du KC, Kuchroo M, Burkhardt DB, Tong A, Israel G, Robert ME, Weisberg SP, Kirkiles-Smith N, Stamatouli AM, Kluger HM, Quandt Z, Young A, Yang ML, Mamula MJ, Pober JS, Anderson MS, Krishnaswamy S, Herold KC. Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes. JCI Insight 2022, 7: e156330. PMID: 35925682, PMCID: PMC9536276, DOI: 10.1172/jci.insight.156330.Peer-Reviewed Original ResearchConceptsCheckpoint inhibitorsΒ-cellsPD-1/PD-L1 pathwayT-lymphocyte antigen-4PD-1 blockadePD-L1 pathwayDeath ligand 1NOD mouse modelDevelopment of diabetesHuman β-cellsAutoimmune complicationsNOD miceΒ-cell populationDeath-1Diabetes mellitusImmune infiltratesInflammatory mediatorsPancreatic inflammationPD-L1Induced diabetesLymphocytic infiltrationInflammatory cytokinesAntigen-4Immune cellsT cells
2021
Differential inflammatory responses of the native left and right ventricle associated with donor heart preservation
Lei I, Huang W, Ward PA, Pober JS, Tellides G, Ailawadi G, Pagani FD, Landstrom AP, Wang Z, Mortensen RM, Cascalho M, Platt J, Chen Y, Lam HYK, Tang PC. Differential inflammatory responses of the native left and right ventricle associated with donor heart preservation. Physiological Reports 2021, 9: e15004. PMID: 34435466, PMCID: PMC8387788, DOI: 10.14814/phy2.15004.Peer-Reviewed Original ResearchConceptsRight ventricleCold ischemiaIL-10Inflammatory responseIL-6 protein levelsCold ischemic preservationEx vivo ischemiaLeft ventricle dysfunctionCold ischemic timeDonor heart preservationInflammatory cytokine expressionCell deathDifferential inflammatory responseTumor necrosis factorComparable inflammatory responsesHuman donor heartsCaspase-3 expressionIschemic preservationVentricle dysfunctionInflammasome expressionIschemic timeRNA sequencingContractile dysfunctionDonor heartsWarm perfusion
2020
Complement activated interferon-γ-primed human endothelium transpresents interleukin-15 to CD8+ T cells
Xie CB, Jiang B, Qin L, Tellides G, Kirkiles-Smith NC, Jane-wit D, Pober JS. Complement activated interferon-γ-primed human endothelium transpresents interleukin-15 to CD8+ T cells. Journal Of Clinical Investigation 2020, 130: 3437-3452. PMID: 32191642, PMCID: PMC7324183, DOI: 10.1172/jci135060.Peer-Reviewed Original ResearchConceptsIL-15/IL-15Rα complexesIL-1βHuman endothelial cellsMembrane attack complexEndothelial cellsAcute rejectionT cellsT cell-mediated acute rejectionCell-mediated acute rejectionComplement-mediated pathologiesIL-15Rα expressionGraft endothelial cellsHuman coronary artery graftsEffector memory CD4T cell infiltrationCoronary artery graftsIL-1 receptorActive IL-1βCultured human endothelial cellsNLRP3 inflammasome assemblyNoncanonical NF-κBArtery graftAlloreactive CD8Complement membrane attack complexMemory CD4An 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
Endothelial Cell–Derived Interleukin-18 Released During Ischemia Reperfusion Injury Selectively Expands T Peripheral Helper Cells to Promote Alloantibody Production
Liu L, Fang C, Fu W, Jiang B, Li G, Qin L, Rosenbluth J, Gong G, Xie CB, Yoo P, Tellides G, Pober JS, Jane-Wit D. Endothelial Cell–Derived Interleukin-18 Released During Ischemia Reperfusion Injury Selectively Expands T Peripheral Helper Cells to Promote Alloantibody Production. Circulation 2019, 141: 464-478. PMID: 31744330, PMCID: PMC7035199, DOI: 10.1161/circulationaha.119.042501.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDelayed Graft FunctionFemaleGene Expression RegulationHuman Umbilical Vein Endothelial CellsHumansImmunoglobulin MInflammasomesInterleukin-18Interleukin-18 Receptor alpha SubunitIsoantibodiesMiceMice, SCIDOrgan TransplantationReperfusion InjurySignal TransductionT-Lymphocytes, Helper-InducerConceptsIschemia-reperfusion injuryDonor-specific antibodiesPeripheral helper cellsIL-18Helper cellsReperfusion injuryInterleukin-18IL-18R1Donor-specific antibody formationEndothelial cellsDelayed graft functionLate allograft lossT cell populationsAlloantibody productionAllograft lossChronic rejectionGraft functionClinical manifestationsPD-L2Antibody formationHumanized modelAllograft tissueImmunoglobulin MPatient specimensComplement activationEndothelial TGF-β signalling drives vascular inflammation and atherosclerosis
Chen PY, Qin L, Li G, Wang Z, Dahlman JE, Malagon-Lopez J, Gujja S, Cilfone N, Kauffman K, Sun L, Sun H, Zhang X, Aryal B, Canfran-Duque A, Liu R, Kusters P, Sehgal A, Jiao Y, Anderson D, Gulcher J, Fernandez-Hernando C, Lutgens E, Schwartz M, Pober J, Chittenden T, Tellides G, Simons M. Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis. Nature Metabolism 2019, 1: 912-926. PMID: 31572976, PMCID: PMC6767930, DOI: 10.1038/s42255-019-0102-3.Peer-Reviewed Original ResearchConceptsTGF-β signalingVascular inflammationDisease progressionPlaque growthProgressive vascular diseaseVessel wall inflammationChronic inflammatory responseSpecific therapeutic interventionsAtherosclerotic plaque growthHyperlipidemic micePlaque inflammationWall inflammationProinflammatory effectsVascular diseaseInflammatory responseVascular permeabilityAtherosclerotic plaquesAbnormal shear stressTherapeutic interventionsInflammationEndothelial TGFΒ signalingVessel wallAtherosclerosisLipid retention
2016
Complement C5 Inhibition Reduces T Cell–Mediated Allograft Vasculopathy Caused by Both Alloantibody and Ischemia Reperfusion Injury in Humanized Mice
Qin L, Li G, Kirkiles‐Smith N, Clark P, Fang C, Wang Y, Yu Z, Devore D, Tellides G, Pober J, Jane‐Wit D. Complement C5 Inhibition Reduces T Cell–Mediated Allograft Vasculopathy Caused by Both Alloantibody and Ischemia Reperfusion Injury in Humanized Mice. American Journal Of Transplantation 2016, 16: 2865-2876. PMID: 27104811, PMCID: PMC5075274, DOI: 10.1111/ajt.13834.Peer-Reviewed Original ResearchConceptsIschemia-reperfusion injuryAllograft vasculopathyEndothelial cell activationReperfusion injuryCell activationComplement C5 inhibitionNuclear factor kappa BSolid organ transplantsT cell infiltrationTerminal complement activationVCAM-1 expressionComplement C5 activationFactor kappa BNeutrophil infiltrationHumanized miceDiffuse stenosisIntraluminal thrombosisArterial graftsC5 inhibitionCell infiltrationHumanized modelNeointimal hyperplasiaOrgan transplantsAlloantibodiesNF-kB
2015
Efficient Gene Disruption in Cultured Primary Human Endothelial Cells by CRISPR/Cas9
Abrahimi P, Chang WG, Kluger MS, Qyang Y, Tellides G, Saltzman WM, Pober JS. Efficient Gene Disruption in Cultured Primary Human Endothelial Cells by CRISPR/Cas9. Circulation Research 2015, 117: 121-128. PMID: 25940550, PMCID: PMC4490936, DOI: 10.1161/circresaha.117.306290.Peer-Reviewed Original ResearchAnimalsCD4-Positive T-LymphocytesCell SeparationCells, CulturedCRISPR-Cas SystemsEndothelial Progenitor CellsFemaleFetal BloodGene DeletionGene Knockout TechniquesGenes, MHC Class IIGenetic VectorsHLA-DR AntigensHumansIntracellular Signaling Peptides and ProteinsLentivirusLymphocyte ActivationLymphocyte Culture Test, MixedMiceMice, SCIDNuclear ProteinsPrimary Cell CultureProteinsTetracyclineTrans-ActivatorsVesicular Transport Proteins
2013
Sustained delivery of proangiogenic microRNA‐132 by nanoparticle transfection improves endothelial cell transplantation
Devalliere J, Chang WG, Andrejecsk JW, Abrahimi P, Cheng CJ, Jane‐wit D, Saltzman WM, Pober JS. Sustained delivery of proangiogenic microRNA‐132 by nanoparticle transfection improves endothelial cell transplantation. The FASEB Journal 2013, 28: 908-922. PMID: 24221087, PMCID: PMC3898640, DOI: 10.1096/fj.13-238527.Peer-Reviewed Original ResearchConceptsHuman umbilical vein ECsEndothelial cellsMiR-132MicroRNA-132Cultured human umbilical vein endothelial cellsNumber of microvesselsGrowth factor-induced proliferationHuman umbilical vein endothelial cellsUmbilical vein endothelial cellsEndothelial cell transplantationCultured endothelial cellsEndogenous growth factorsEC transplantationVein endothelial cellsCell transplantationImmunodeficient miceTissue perfusionTransplantationMiR deliveryGrowth factorIntegrin αvβ3Endocytosed nanoparticlesSquare millimeterBiological effectsControl transfectionAlloantibody 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
2011
Transforming Growth Factor Beta Expression by Human Vascular Cells Inhibits Interferon Gamma Production and Arterial Media Injury by Alloreactive Memory T Cells
Lebastchi AH, Khan SF, Qin L, Li W, Zhou J, Hibino N, Yi T, Rao DA, Pober JS, Tellides G. Transforming Growth Factor Beta Expression by Human Vascular Cells Inhibits Interferon Gamma Production and Arterial Media Injury by Alloreactive Memory T Cells. American Journal Of Transplantation 2011, 11: 2332-2341. PMID: 21812925, PMCID: PMC3203343, DOI: 10.1111/j.1600-6143.2011.03676.x.Peer-Reviewed Original ResearchConceptsEffector T cellsMemory T cellsNaïve T cellsT cellsIL-17Vascular cellsEffector memory T cellsAlloreactive memory T cellsGrowth factor-beta expressionMedial smooth muscle cellsHuman effector memory T cellsHuman coronary artery graftsIL-17 productionCoronary artery graftsIFN-γ productionAllogeneic endothelial cellsInterferon-gamma productionDevelopment of arteriosclerosisExpression of TGFRole of TGFSmooth muscle cellsImmunodeficient mouse hostsHuman T cellsIntimal compartmentMedial infiltration