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-lifeIdentification and validation of urinary CXCL9 as a biomarker for diagnosis of acute interstitial nephritis
Moledina D, Obeid W, Smith R, Rosales I, Sise M, Moeckel G, Kashgarian M, Kuperman M, Campbell K, Lefferts S, Meliambro K, Bitzer M, Perazella M, Luciano R, Pober J, Cantley L, Colvin R, Wilson F, Parikh C. Identification and validation of urinary CXCL9 as a biomarker for diagnosis of acute interstitial nephritis. Journal Of Clinical Investigation 2024, 134: e180583. PMID: 38488004, PMCID: PMC10940080, DOI: 10.1172/jci180583.Peer-Reviewed Original Research
2023
Multiscale genetic architecture of donor-recipient differences reveals intronic LIMS1 mismatches associated with kidney transplant survival
Sun Z, Zhang Z, Banu K, Gibson I, Colvin R, Yi Z, Zhang W, De Kumar B, Reghuvaran A, Pell J, Manes T, Djamali A, Gallon L, O'Connell P, He J, Pober J, Heeger P, Menon M. Multiscale genetic architecture of donor-recipient differences reveals intronic LIMS1 mismatches associated with kidney transplant survival. Journal Of Clinical Investigation 2023, 133: e170420. PMID: 37676733, PMCID: PMC10617779, DOI: 10.1172/jci170420.Peer-Reviewed Original ResearchConceptsDeath-censored graft lossHuman leukocyte antigenExpression quantitative trait lociT cellsTGF-β1TGF-β1/Smad pathwayDonor-recipient differencesKidney allograft lossChronic allograft rejectionKidney transplant survivalDonor-recipient mismatchActive TGF-β1Allograft lossGraft lossAllograft rejectionTransplant cohortPeripheral bloodLeukocyte antigenClinical trialsImmune cellsHaplotype mismatchGenome-wide scaleTransplant survivalQuantitative trait lociSingle nucleotide polymorphism dataHedgehog 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 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 genesIdentification and validation of urinary CXCL9 as a biomarker for diagnosis of acute interstitial nephritis
Moledina D, Obeid W, Smith R, Rosales I, Sise M, Moeckel G, Kashgarian M, Kuperman M, Campbell K, Lefferts S, Meliambro K, Bitzer M, Perazella M, Luciano R, Pober J, Cantley L, Colvin R, Wilson F, Parikh C. Identification and validation of urinary CXCL9 as a biomarker for diagnosis of acute interstitial nephritis. Journal Of Clinical Investigation 2023, 133: e168950. PMID: 37395276, PMCID: PMC10313360, DOI: 10.1172/jci168950.Peer-Reviewed Original ResearchConceptsUrinary CXCL9External validation cohortValidation cohortControl groupAIN diagnosisDiscovery cohortKidney tissueDiagnostic biomarkersAcute interstitial nephritisCXCL9 mRNA expressionAcute kidney injuryBiopsy-confirmed diagnosisAvailable clinical testsNational InstituteKidney injuryTubulointerstitial nephritisInterstitial nephritisKidney biopsyHistological confirmationHistological diagnosisTreatment optionsLymphocyte chemotaxisCXCL9MRNA expression differencesPatientsA 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 ResearchConceptsSingle-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 ResearchConceptsIntegrated 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 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
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 ResearchConceptsTargeted 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 ResearchConceptsT 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 CD4Immune 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 cellsNative human collagen type I provides a viable physiologically relevant alternative to xenogeneic sources for tissue engineering applications: A comparative in vitro and in vivo study
Baltazar T, Kajave NS, Rodriguez M, Chakraborty S, Jiang B, Skardal A, Kishore V, Pober JS, Albanna MZ. Native human collagen type I provides a viable physiologically relevant alternative to xenogeneic sources for tissue engineering applications: A comparative in vitro and in vivo study. Journal Of Biomedical Materials Research Part B Applied Biomaterials 2022, 110: 2323-2337. PMID: 35532208, PMCID: PMC11103545, DOI: 10.1002/jbm.b.35080.Peer-Reviewed Original ResearchWanted: 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 deliveryDeliveryComorbiditiesTransplantGraftInjuryPerfusionVasculatureArhGEF12 activates Rap1A and not RhoA in human dermal microvascular endothelial cells to reduce tumor necrosis factor‐induced leak
Khan A, Ni W, Baltazar T, Lopez‐Giraldez F, Pober JS, Pierce RW. ArhGEF12 activates Rap1A and not RhoA in human dermal microvascular endothelial cells to reduce tumor necrosis factor‐induced leak. The FASEB Journal 2022, 36: e22254. PMID: 35294066, PMCID: PMC9103844, DOI: 10.1096/fj.202101873rr.Peer-Reviewed Original Research