2024
Nanoscale Surface Topography of Polyethylene Glycol-Coated Nanoparticles Composed of Bottlebrush Block Copolymers Prolongs Systemic Circulation and Enhances Tumor Uptake
Grundler J, Shin K, Suh H, Whang C, Fulgoni G, Pierce R, Saltzman W. Nanoscale Surface Topography of Polyethylene Glycol-Coated Nanoparticles Composed of Bottlebrush Block Copolymers Prolongs Systemic Circulation and Enhances Tumor Uptake. ACS Nano 2024, 18: 2815-2827. PMID: 38227820, DOI: 10.1021/acsnano.3c05921.Peer-Reviewed Original ResearchConceptsBottlebrush block copolymersSurface topographyBlock copolymersPoly(ethylene glycolClinical translation of nanomedicinePEGylated nanoparticlesEnhanced tumor uptakeNanoscale surface topographyTranslation of nanomedicinesRough surface topographyLinear block copolymersProlonged systemic circulationPerformance of nanocarriersPolymer coatingNanoparticle coatingSmooth surfaced nanoparticlesTumor uptakeTumor accumulationBiomedical applicationsNanoparticle formulationSystemic circulationClinical translationTumor extravasationNanoparticlesCoating
2023
MicroRNA-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 formAn AI-powered patient triage platform for future viral outbreaks using COVID-19 as a disease model
Charkoftaki G, Aalizadeh R, Santos-Neto A, Tan W, Davidson E, Nikolopoulou V, Wang Y, Thompson B, Furnary T, Chen Y, Wunder E, Coppi A, Schulz W, Iwasaki A, Pierce R, Cruz C, Desir G, Kaminski N, Farhadian S, Veselkov K, Datta R, Campbell M, Thomaidis N, Ko A, Thompson D, Vasiliou V. An AI-powered patient triage platform for future viral outbreaks using COVID-19 as a disease model. Human Genomics 2023, 17: 80. PMID: 37641126, PMCID: PMC10463861, DOI: 10.1186/s40246-023-00521-4.Peer-Reviewed Original ResearchConceptsCOVID-19 patientsDisease severityViral outbreaksFuture viral outbreaksLength of hospitalizationIntensive care unitWorse disease prognosisLife-threatening illnessEffective medical interventionsCOVID-19Clinical decision treeGlucuronic acid metabolitesNew potential biomarkersHospitalization lengthCare unitComorbidity dataSerotonin levelsDisease progressionHealthy controlsPatient outcomesDisease prognosisPatient transferPatientsHealthcare resourcesPotential biomarkersSingle-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 cells
2022
A retrospective cohort analysis of the Yale pediatric genomics discovery program
Al‐Ali S, Jeffries L, Faustino EVS, Ji W, Mis E, Konstantino M, Zerillo C, Jiang Y, Spencer‐Manzon M, Bale A, Zhang H, McGlynn J, McGrath JM, Tremblay T, Brodsky NN, Lucas CL, Pierce R, Deniz E, Khokha MK, Lakhani SA. A retrospective cohort analysis of the Yale pediatric genomics discovery program. American Journal Of Medical Genetics Part A 2022, 188: 2869-2878. PMID: 35899841, PMCID: PMC9474639, DOI: 10.1002/ajmg.a.62918.Peer-Reviewed Original ResearchConceptsRetrospective cohort analysisNext-generation sequencingCohort analysisSystem abnormalitiesImmune system abnormalitiesCardiovascular system abnormalitiesFunctional molecular analysesNovel genesPrecise molecular diagnosisClinical characteristicsFurther genetic evaluationDiscovery programsComplex patientsMultisystem diseaseDisease genesPediatric providersRare genetic diseaseNew diagnosisPhenotype relationshipsPatientsGenetic diseasesMolecular analysisDiagnosisParticipant demographicsNGS resultsArhGEF12 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 ResearchPediatric Organ Dysfunction Information Update Mandate (PODIUM) Contemporary Organ Dysfunction Criteria: Executive Summary.
Bembea MM, Agus M, Akcan-Arikan A, Alexander P, Basu R, Bennett TD, Bohn D, Brandão LR, Brown AM, Carcillo JA, Checchia P, Cholette J, Cheifetz IM, Cornell T, Doctor A, Eckerle M, Erickson S, Farris RWD, Faustino EVS, Fitzgerald JC, Fuhrman DY, Giuliano JS, Guilliams K, Gaies M, Gorga SM, Hall M, Hanson SJ, Hartman M, Hassinger AB, Irving SY, Jeffries H, Jouvet P, Kannan S, Karam O, Khemani RG, Kissoon N, Lacroix J, Laussen P, Leclerc F, Lee JH, Leteurtre S, Lobner K, McKiernan PJ, Menon K, Monagle P, Muszynski JA, Odetola F, Parker R, Pathan N, Pierce RW, Pineda J, Prince JM, Robinson KA, Rowan CM, Ryerson LM, Sanchez-Pinto LN, Schlapbach LJ, Selewski DT, Shekerdemian LS, Simon D, Smith LS, Squires JE, Squires RH, Sutherland SM, Ouellette Y, Spaeder MC, Srinivasan V, Steiner ME, Tasker RC, Thiagarajan R, Thomas N, Tissieres P, Traube C, Tucci M, Typpo KV, Wainwright MS, Ward SL, Watson RS, Weiss S, Whitney J, Willson D, Wynn JL, Yehya N, Zimmerman JJ. Pediatric Organ Dysfunction Information Update Mandate (PODIUM) Contemporary Organ Dysfunction Criteria: Executive Summary. Pediatrics 2022, 149: s1-s12. PMID: 34970673, PMCID: PMC9599725, DOI: 10.1542/peds.2021-052888b.Peer-Reviewed Original ResearchConceptsMultiple organ dysfunctionOrgan dysfunctionIll childrenElectronic data extraction formSingle organ dysfunctionPrognosis Studies toolRisk of biasImmune system dysfunctionMedical Subject Headings termsEvidence-based criteriaData extraction formSubject Headings termsAcute liverSystem dysfunctionClinical assessmentElectronic searchDysfunctionExtraction formSystematic reviewAvailable evidenceExpert panelMeaningful outcomesStudy identificationChildrenStudy toolEndothelial Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.
Pierce RW, Giuliano JS, Whitney JE, Ouellette Y. Endothelial Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference. Pediatrics 2022, 149: s97-s102. PMID: 34970676, PMCID: PMC9754809, DOI: 10.1542/peds.2021-052888o.Peer-Reviewed Original ResearchConceptsMultiple organ dysfunction syndromeOrgan dysfunction syndromeEndothelial dysfunctionIll childrenDysfunction syndromeEndothelial functionPediatric multiple organ dysfunction syndromeVascular segmentsOrgan systemsStandard data extraction formOrgan-specific outcomesPediatric critical illnessPODIUM Consensus ConferencePatient-centered outcomesNon-English language studiesCombination of biomarkersData extraction formStudies of adultsCritical illnessCase seriesPremature infantsFunctional statusEligible studiesBias assessmentLeukocyte recruitment
2021
Integrated Single-Cell Atlas of Endothelial Cells of the Human Lung
Schupp JC, Adams TS, Cosme C, Raredon MSB, Yuan Y, Omote N, Poli S, Chioccioli M, Rose KA, Manning EP, Sauler M, DeIuliis G, Ahangari F, Neumark N, Habermann AC, Gutierrez AJ, Bui LT, Lafyatis R, Pierce RW, Meyer KB, Nawijn MC, Teichmann SA, Banovich NE, Kropski JA, Niklason LE, Pe’er D, Yan X, Homer RJ, Rosas IO, Kaminski N. Integrated Single-Cell Atlas of Endothelial Cells of the Human Lung. Circulation 2021, 144: 286-302. PMID: 34030460, PMCID: PMC8300155, DOI: 10.1161/circulationaha.120.052318.Peer-Reviewed Original ResearchConceptsDifferential expression analysisPrimary lung endothelial cellsLung endothelial cellsCell typesMarker genesExpression analysisSingle-cell RNA sequencing dataCross-species analysisVenous endothelial cellsEndothelial marker genesSingle-cell atlasMarker gene setsRNA sequencing dataEndothelial cellsSubsequent differential expression analysisDifferent lung cell typesResident cell typesLung cell typesCellular diversityEndothelial cell typesCapillary endothelial cellsHuman lung endothelial cellsPhenotypic diversityEndothelial diversityIndistinguishable populationsTumor necrosis factor‐induced ArhGEF10 selectively activates RhoB contributing to human microvascular endothelial cell tight junction disruption
Khan A, Ni W, Lopez‐Giraldez F, Kluger MS, Pober JS, Pierce RW. Tumor necrosis factor‐induced ArhGEF10 selectively activates RhoB contributing to human microvascular endothelial cell tight junction disruption. The FASEB Journal 2021, 35: e21627. PMID: 33948992, PMCID: PMC9026622, DOI: 10.1096/fj.202002783rr.Peer-Reviewed Original ResearchConceptsCapillary endothelial cellsHuman dermal microvascular endothelial cellsMicrovascular endothelial cellsEndothelial cellsTight junctionsCultured human microvascular endothelial cellsEC tight junctionsLoss of barrierCapillary leak syndromeCapillary barrier functionDermal microvascular endothelial cellsRhoB activationTight junction disruptionDisrupts tight junctionsHuman microvascular endothelial cellsExtent of TNFHuman capillary endothelial cellsLeak syndromeOverwhelming inflammationCapillary leakBarrier lossTJ disruptionJunction disruptionRhoB knockdownTNFPazopanib ameliorates acute lung injuries via inhibition of MAP3K2 and MAP3K3
Yuan Q, Basit A, Liang W, Qu R, Luan Y, Ren C, Li A, Xu X, Liu X, Yang C, Kuo A, Pierce R, Zhang L, Turk B, Hu X, Li F, Cui W, Li R, Huang D, Mo L, Sessa WC, Lee PJ, Kluger Y, Su B, Tang W, He J, Wu D. Pazopanib ameliorates acute lung injuries via inhibition of MAP3K2 and MAP3K3. Science Translational Medicine 2021, 13 PMID: 33910977, PMCID: PMC8466683, DOI: 10.1126/scitranslmed.abc2499.Peer-Reviewed Original ResearchConceptsAcute lung injuryLung injuryMyeloid cellsLung transplantation recipientsMouse ALI modelPulmonary barrier functionTransplantation recipientsALI modelReactive oxygen species formationPharmacological interventionsPazopanibOxygen species formationVasculature integrityEpithelial cell survivalHigh mortalityMitogen-activated protein kinase kinase kinase 2Barrier functionGenetic inactivationInjuryCell survivalMortalityProtein kinase kinase kinase 2MAP3K3Kinase 2ManifestationsImmune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children
Ramaswamy A, Brodsky NN, Sumida TS, Comi M, Asashima H, Hoehn KB, Li N, Liu Y, Shah A, Ravindra NG, Bishai J, Khan A, Lau W, Sellers B, Bansal N, Guerrerio P, Unterman A, Habet V, Rice AJ, Catanzaro J, Chandnani H, Lopez M, Kaminski N, Dela Cruz CS, Tsang JS, Wang Z, Yan X, Kleinstein SH, van Dijk D, Pierce RW, Hafler DA, Lucas CL. Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children. Immunity 2021, 54: 1083-1095.e7. PMID: 33891889, PMCID: PMC8043654, DOI: 10.1016/j.immuni.2021.04.003.Peer-Reviewed Original ResearchConceptsMIS-C patientsDisease severityInflammatory syndromeTCR repertoireSARS-CoV-2-associated multisystem inflammatory syndromeAsymptomatic SARS-CoV-2 infectionSARS-CoV-2 infectionAdult COVID-19Post-infectious complicationsMultisystem inflammatory syndromeCytotoxicity genesHealthy pediatricImmune dysregulationMemory TActive infectionMyeloid dysfunctionPatientsSingle-cell RNA sequencingFlow cytometrySerum proteomicsRepertoire analysisElevated expressionSeverityAlarminsCOVID-19Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes
Ravindra NG, Alfajaro MM, Gasque V, Huston NC, Wan H, Szigeti-Buck K, Yasumoto Y, Greaney AM, Habet V, Chow RD, Chen JS, Wei J, Filler RB, Wang B, Wang G, Niklason LE, Montgomery RR, Eisenbarth SC, Chen S, Williams A, Iwasaki A, Horvath TL, Foxman EF, Pierce RW, Pyle AM, van Dijk D, Wilen CB. Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes. PLOS Biology 2021, 19: e3001143. PMID: 33730024, PMCID: PMC8007021, DOI: 10.1371/journal.pbio.3001143.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Human bronchial epithelial cellsInterferon-stimulated genesCell state changesAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionCell tropismCoronavirus 2 infectionCoronavirus disease 2019Onset of infectionCell-intrinsic expressionCourse of infectionAir-liquid interface culturesHost-viral interactionsBronchial epithelial cellsSingle-cell RNA sequencingCell typesIL-1Disease 2019Human airwaysDevelopment of therapeuticsDrug AdministrationViral replication
2018
Sera From Children After Cardiopulmonary Bypass Reduces Permeability of Capillary Endothelial Cell Barriers
Pierce RW, Zahr RA, Kandil S, Faustino EVS, Pober JS. Sera From Children After Cardiopulmonary Bypass Reduces Permeability of Capillary Endothelial Cell Barriers. Pediatric Critical Care Medicine 2018, 19: 609-618. PMID: 29652749, PMCID: PMC6037548, DOI: 10.1097/pcc.0000000000001553.Peer-Reviewed Original ResearchConceptsTransendothelial electrical resistanceCardiopulmonary bypassCapillary endothelial cellsEndothelial cellsCapillary leakPatient seraClaudin-5Pulmonary capillary endothelial cellsBarrier functionPulmonary microvascular endothelial cellsReal-time quantitative reverse transcription polymerase chain reactionTertiary pediatric hospitalQuantitative reverse transcription polymerase chain reactionCardiopulmonary bypass circuitCongenital heart diseaseReverse transcription-polymerase chain reactionTranscription-polymerase chain reactionMicrovascular endothelial cellsEndothelial cell barrierCohort studyInflammatory mediatorsPediatric hospitalUnclear etiologyBarrier disruptionHeart diseaseComplete Recovery After Acute Zonisamide Overdose in an Adolescent Female
McStay C, Pierce R, Riley C. Complete Recovery After Acute Zonisamide Overdose in an Adolescent Female. Pediatric Emergency Care 2018, 34: e30-e31. PMID: 27749631, DOI: 10.1097/pec.0000000000000854.Peer-Reviewed Original ResearchConceptsElectrocardiographic abnormalitiesPartial seizuresEndotracheal intubationMechanical ventilationIntentional ingestionCase reportCatecholamine infusionMood disordersSingle agentComplete recoveryZonisamideAdolescent femalesIngestionSulfonamide drugsReportIntubationComplicationsPatientsOverdoseSeizuresInfusionAbnormalitiesWomen
2017
A p190BRhoGAP mutation and prolonged RhoB activation in fatal systemic capillary leak syndrome
Pierce RW, Merola J, Lavik JP, Kluger MS, Huttner A, Khokha MK, Pober JS. A p190BRhoGAP mutation and prolonged RhoB activation in fatal systemic capillary leak syndrome. Journal Of Experimental Medicine 2017, 214: 3497-3505. PMID: 29097442, PMCID: PMC5716031, DOI: 10.1084/jem.20162143.Peer-Reviewed Original ResearchConceptsTumor necrosis factorSystemic capillary leakDermal microvascular endothelial cellsMicrovascular endothelial cellsPatient-derived endothelial cellsEndothelial cellsCapillary leakNormal human dermal microvascular endothelial cellsSystemic capillary leak syndromeBarrier functionCapillary leak syndromeHuman dermal microvascular endothelial cellsTransendothelial electrical resistanceEC barrier functionNormal endothelial cellsLeak syndromeCritical illnessFatal casesNecrosis factorBarrier recoverySiRNA knockdownEC culturesRhoB activationGreater increaseJunctional proteinsEndothelial Cell Function and Dysfunction in Critically Ill Children
Pierce RW, Giuliano JS, Pober JS. Endothelial Cell Function and Dysfunction in Critically Ill Children. Pediatrics 2017, 140: e20170355. PMID: 28759412, PMCID: PMC9923607, DOI: 10.1542/peds.2017-0355.Peer-Reviewed Original ResearchConceptsEndothelial cellsCritical illnessIll childrenCritically Ill ChildrenImmune cell recruitmentBiology of ECsEndothelial cell functionBroad anatomic distributionEntire vascular systemPathologic responseAnatomic distributionClinical correlationMaintenance of homeostasisBlood flowCell recruitmentBlood fluiditySystemic homeostasisCell functionSegmental differencesEC functionVascular systemIllnessChildrenHomeostasisSpecific role
2016
IL-17 Promotes Neutrophil-Mediated Immunity by Activating Microvascular Pericytes and Not Endothelium
Liu R, Lauridsen HM, Amezquita RA, Pierce RW, Jane-Wit D, Fang C, Pellowe AS, Kirkiles-Smith NC, Gonzalez AL, Pober JS. IL-17 Promotes Neutrophil-Mediated Immunity by Activating Microvascular Pericytes and Not Endothelium. The Journal Of Immunology 2016, 197: 2400-2408. PMID: 27534549, PMCID: PMC5010945, DOI: 10.4049/jimmunol.1600138.Peer-Reviewed Original ResearchMeSH KeywordsCaspase 9Cells, CulturedCulture MediaCytokinesEndothelium, VascularGranulocyte Colony-Stimulating FactorGranulocyte-Macrophage Colony-Stimulating FactorHumansInterleukin-17Neutrophil InfiltrationNeutrophilsPericytesReceptors, Interleukin-17Sequence Analysis, RNATumor Necrosis Factor-alphaVenulesConceptsIL-17Endothelial cellsIL-17RAIL-17RC subunitsCultured human endothelial cellsInflammatory gene expressionMicrovascular endothelial cellsNeutrophil-mediated immunityNeutrophil infiltrationNeutrophilic inflammationHuman endothelial cellsAcute inflammationIL-1βNeutrophil functionProinflammatory cytokinesIL-8Proinflammatory moleculesIL-1αIL-17RCIL-1Human pericytesG-CSFMicrovascular pericytesNeutrophil productionNeutrophil survivalAssociation of thrombophilia and catheter‐associated thrombosis in children: a systematic review and meta‐analysis
Neshat‐Vahid S, Pierce R, Hersey D, Raffini LJ, Faustino EV. Association of thrombophilia and catheter‐associated thrombosis in children: a systematic review and meta‐analysis. Journal Of Thrombosis And Haemostasis 2016, 14: 1749-1758. PMID: 27306795, PMCID: PMC5035642, DOI: 10.1111/jth.13388.Peer-Reviewed Original ResearchConceptsDeep vein thrombosisCatheter-associated thrombosisCentral venous catheter useElevated factor VIII levelsAssociation of thrombophiliaRoutine thrombophilia testingVenous catheter useCochrane Central RegisterPediatric risk factorsPooled prevalence rateFactor VIII levelsProtein C deficiencyRandom-effects modelWeb of ScienceThrombophilic traitsCatheter useCentral RegisterCohort studyFV Leiden mutationVein thrombosisControlled TrialsVenous thrombosisPediatric studiesRisk factorsOdds ratio