Featured Publications
Macrophage migration inhibitory factor deficiency in chronic obstructive pulmonary disease
Sauler M, Leng L, Trentalange M, Haslip M, Shan P, Piecychna M, Zhang Y, Andrews N, Mannam P, Allore H, Fried T, Bucala R, Lee PJ. Macrophage migration inhibitory factor deficiency in chronic obstructive pulmonary disease. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2014, 306: l487-l496. PMID: 24441872, PMCID: PMC3949087, DOI: 10.1152/ajplung.00284.2013.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAge FactorsAgedAged, 80 and overAnimalsApoptosisCellular SenescenceCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p21EmphysemaFemaleHumansIntramolecular OxidoreductasesLungMacrophage Migration-Inhibitory FactorsMaleMiceMice, Inbred C57BLMice, KnockoutMiddle AgedPulmonary Disease, Chronic ObstructiveReceptors, ImmunologicSmokeSmokingTobaccoTumor Suppressor Protein p53Young AdultConceptsChronic obstructive pulmonary diseaseMacrophage migration inhibitory factorPathogenesis of COPDDevelopment of COPDMIF receptor CD74Obstructive pulmonary diseasePulmonary diseaseWT miceReceptor CD74Role of MIFMacrophage migration inhibitory factor deficiencyMigration inhibitory factorNormal alveolar structureMo of ageWild-type controlsMIF concentrationsFormer smokersLung volumePlasma concentrationsSpontaneous emphysemaFactor deficiencyCigarette smokePleiotropic cytokineInhibitory factorAlveolar structuresEndothelial CD74 mediates macrophage migration inhibitory factor protection in hyperoxic lung injury
Sauler M, Zhang Y, Min J, Leng L, Shan P, Roberts S, Jorgensen WL, Bucala R, Lee PJ. Endothelial CD74 mediates macrophage migration inhibitory factor protection in hyperoxic lung injury. The FASEB Journal 2015, 29: 1940-1949. PMID: 25609432, PMCID: PMC4415022, DOI: 10.1096/fj.14-260299.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorLung endothelial cellsMurine lung endothelial cellsLung injuryEndothelial cellsProtective effectExogenous MIFCD74 deficient miceCD74-dependent mannerHours of hyperoxiaMIF receptor CD74Acute lung injuryHyperoxic lung injuryBronchoalveolar lavage proteinMigration inhibitory factorBronchoalveolar proteinMIF deficiencyMedian survivalEndothelial injuryWT miceAcute oxidative stressReceptor CD74Lavage proteinReceptor antagonistReceptor inhibitorsThe DNA repair transcriptome in severe COPD
Sauler M, Lamontagne M, Finnemore E, Herazo-Maya JD, Tedrow J, Zhang X, Morneau JE, Sciurba F, Timens W, Paré PD, Lee PJ, Kaminski N, Bossé Y, Gomez JL. The DNA repair transcriptome in severe COPD. European Respiratory Journal 2018, 52: 1701994. PMID: 30190272, PMCID: PMC6422831, DOI: 10.1183/13993003.01994-2017.Peer-Reviewed Original ResearchConceptsDNA damage toleranceDNA repairInadequate DNA repairSevere chronic obstructive pulmonary diseaseChronic obstructive pulmonary diseaseRepair pathwaysGene correlation network analysisIntegrative genomics approachNucleotide excision repair pathwayDNA repair pathwaysGene Set Enrichment AnalysisExcision repair pathwayGlobal transcriptomic profilesDNA repair genesDNA repair responseCorrelation network analysisCOPD severityGenomic approachesLung tissue transcriptomeTranscriptomic differencesTranscriptomic changesTranscriptomic patternsRNA sequencingTissue transcriptomesTranscriptomic profilesMicroRNA miR-24-3p reduces DNA damage responses, apoptosis, and susceptibility to chronic obstructive pulmonary disease
Nouws J, Wan F, Finnemore E, Roque W, Kim SJ, Bazan IS, Li CX, Sköld C, Dai Q, Yan X, Chioccioli M, Neumeister V, Britto CJ, Sweasy J, Bindra RS, Wheelock ÅM, Gomez JL, Kaminski N, Lee PJ, Sauler M. MicroRNA miR-24-3p reduces DNA damage responses, apoptosis, and susceptibility to chronic obstructive pulmonary disease. JCI Insight 2021, 6: e134218. PMID: 33290275, PMCID: PMC7934877, DOI: 10.1172/jci.insight.134218.Peer-Reviewed Original ResearchConceptsCellular stress responseStress responseHomology-directed DNA repairDNA damage responseProtein BRCA1Damage responseCellular stressDNA repairProtein BimCOPD lung tissueLung epithelial cellsCellular responsesExpression arraysEpithelial cell apoptosisDNA damageChronic obstructive pulmonary diseaseBRCA1 expressionCell apoptosisApoptosisEpithelial cellsCritical mechanismMicroRNAsRegulatorObstructive pulmonary diseaseIncreases SusceptibilityCharacterization of the COPD alveolar niche using single-cell RNA sequencing
Sauler M, McDonough JE, Adams TS, Kothapalli N, Barnthaler T, Werder RB, Schupp JC, Nouws J, Robertson MJ, Coarfa C, Yang T, Chioccioli M, Omote N, Cosme C, Poli S, Ayaub EA, Chu SG, Jensen KH, Gomez JL, Britto CJ, Raredon MSB, Niklason LE, Wilson AA, Timshel PN, Kaminski N, Rosas IO. Characterization of the COPD alveolar niche using single-cell RNA sequencing. Nature Communications 2022, 13: 494. PMID: 35078977, PMCID: PMC8789871, DOI: 10.1038/s41467-022-28062-9.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingRNA sequencingCell-specific mechanismsChronic obstructive pulmonary diseaseAdvanced chronic obstructive pulmonary diseaseTranscriptomic network analysisSingle-cell RNA sequencing profilesCellular stress toleranceAberrant cellular metabolismStress toleranceRNA sequencing profilesTranscriptional evidenceCellular metabolismAlveolar nicheSequencing profilesHuman alveolar epithelial cellsChemokine signalingAlveolar epithelial type II cellsObstructive pulmonary diseaseSitu hybridizationType II cellsEpithelial type II cellsSequencingCOPD pathobiologyHuman lung tissue samples
2023
A statistical framework to identify cell types whose genetically regulated proportions are associated with complex diseases
Liu W, Deng W, Chen M, Dong Z, Zhu B, Yu Z, Tang D, Sauler M, Lin C, Wain L, Cho M, Kaminski N, Zhao H. A statistical framework to identify cell types whose genetically regulated proportions are associated with complex diseases. PLOS Genetics 2023, 19: e1010825. PMID: 37523391, PMCID: PMC10414598, DOI: 10.1371/journal.pgen.1010825.Peer-Reviewed Original ResearchConceptsCell typesDisease-associated tissuesWide association studyComplex diseasesCell type proportionsDisease-relevant tissuesReal GWAS dataFunctional genesTranscriptomic dataGWAS dataGenetic dataAssociation studiesNovel statistical frameworkChronic obstructive pulmonary diseaseStatistical frameworkObstructive pulmonary diseaseIdiopathic pulmonary fibrosisBreast cancer riskType proportionsBlood CD8Pulmonary diseasePulmonary fibrosisPredictive biomarkersLung tissueBreast cancer
2022
Compromised Cardiopulmonary Function in Fibulin-5 Deficient Mice.
Ramachandra AB, Mikush N, Sauler M, Humphrey JD, Manning EP. Compromised Cardiopulmonary Function in Fibulin-5 Deficient Mice. Journal Of Biomechanical Engineering 2022, 144 PMID: 35171214, PMCID: PMC8990734, DOI: 10.1115/1.4053873.Peer-Reviewed Original ResearchConceptsRight heart functionDeficient micePulmonary arteryHeart functionCompromised right ventricular functionFibulin-5 deficient micePulmonary arterial structureRight ventricular functionVentilation-perfusion relationshipsElastic fiber contentElastic fibersFiber dysfunctionLung compliancePulmonary healthVentricular functionCardiopulmonary functionAlveolar disruptionPulmonary pathologyLung parenchymaMurine modelMouse modelArterial structureHistological quantificationElastic laminaRight circulationSex differences and altered mitophagy in experimental pulmonary hypertension
Bazan IS, Kim SJ, Ardito TA, Zhang Y, Shan P, Sauler M, Lee P. Sex differences and altered mitophagy in experimental pulmonary hypertension. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2022, 322: l761-l769. PMID: 35137625, PMCID: PMC9076415, DOI: 10.1152/ajplung.00019.2020.Peer-Reviewed Original ResearchConceptsPulmonary hypertensionPathogenesis of PHFemale-predominant diseaseRight heart failurePulmonary arterial pressureExperimental pulmonary hypertensionMitochondrial dysfunctionLung endothelial cellsSex differencesMouse lung endothelial cellsInhibition of ParkinArterial pressureHeart failurePulmonary arteryMitochondrial respiratory capacityPoor outcomeHigh prevalenceSevere diseaseAnimal modelsEndothelial cellsParkin expressionOxidative stressCell proliferationHypertensionSex
2021
MIF but not MIF-2 recruits inflammatory macrophages in an experimental polymicrobial sepsis model
Tilstam PV, Schulte W, Holowka T, Kim BS, Nouws J, Sauler M, Piecychna M, Pantouris G, Lolis E, Leng L, Bernhagen J, Fingerle-Rowson G, Bucala R. MIF but not MIF-2 recruits inflammatory macrophages in an experimental polymicrobial sepsis model. Journal Of Clinical Investigation 2021, 131: e127171. PMID: 34850744, PMCID: PMC8631602, DOI: 10.1172/jci127171.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCytokinesDisease Models, AnimalFemaleFlow CytometryGene Expression ProfilingInflammationIntramolecular OxidoreductasesLeukocyte CountMacrophage Migration-Inhibitory FactorsMacrophagesMacrophages, PeritonealMaleMiceMice, Inbred C57BLMice, TransgenicPeritoneal LavagePhenotypeProtein BindingRNA-SeqSepsisSignal TransductionConceptsMacrophage migration inhibitory factorSmall peritoneal macrophagesLarge peritoneal macrophagesPolymicrobial sepsisPeritoneal macrophagesMIF receptor CD74MIF promoter polymorphismsMIF-2Migration inhibitory factorPolymicrobial sepsis modelMIF deficiencyAdoptive transferSeptic shockSurvival benefitInfectious insultsMIF antibodyExcessive inflammationInflammatory cytokinesReceptor CD74Sepsis modelProtective effectPeritoneal cavityDifferent infectionsPromoter polymorphismInflammatory macrophagesMetformin: Experimental and Clinical Evidence for a Potential Role in Emphysema Treatment.
Polverino F, Wu TD, Rojas-Quintero J, Wang X, Mayo J, Tomchaney M, Tram J, Packard S, Zhang D, Cleveland KH, Cordoba-Lanus E, Owen CA, Fawzy A, Kinney GL, Hersh CP, Hansel NN, Doubleday K, Sauler M, Tesfaigzi Y, Ledford JG, Casanova C, Zmijewski J, Konhilas J, Langlais PR, Schnellmann R, Rahman I, McCormack M, Celli B. Metformin: Experimental and Clinical Evidence for a Potential Role in Emphysema Treatment. American Journal Of Respiratory And Critical Care Medicine 2021, 204: 651-666. PMID: 34033525, PMCID: PMC8521702, DOI: 10.1164/rccm.202012-4510oc.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseMetformin useEmphysema progressionEmphysematous chronic obstructive pulmonary diseaseOxidative stressSmall airway remodelingProtective actionEfficacy of metforminObstructive pulmonary diseaseCigarette smoke inhalationPercentage of emphysemaER stressEndoplasmic reticulum stressEmphysema treatmentAirway remodelingPulmonary diseasePulmonary inflammationAirspace enlargementClinical evidenceLung agingAge-related diseasesSmoke inhalationClinical trialsMuscle injuryMetformin effectsSingle-cell characterization of a model of poly I:C-stimulated peripheral blood mononuclear cells in severe asthma
Chen A, Diaz-Soto MP, Sanmamed MF, Adams T, Schupp JC, Gupta A, Britto C, Sauler M, Yan X, Liu Q, Nino G, Cruz CSD, Chupp GL, Gomez JL. Single-cell characterization of a model of poly I:C-stimulated peripheral blood mononuclear cells in severe asthma. Respiratory Research 2021, 22: 122. PMID: 33902571, PMCID: PMC8074196, DOI: 10.1186/s12931-021-01709-9.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsSevere asthmaEffector T cellsBlood mononuclear cellsT cellsHealthy controlsPoly IDendritic cellsMononuclear cellsUnstimulated peripheral blood mononuclear cellsInterferon responseTLR3 agonist poly IImpaired interferon responseMain cell subsetsNatural killer cellsPro-inflammatory profilePro-inflammatory pathwaysC stimulationCyTOF profilingHigh CD8Cell typesEffector cellsKiller cellsCell subsetsMain cell types
2020
Gene coexpression networks reveal novel molecular endotypes in alpha-1 antitrypsin deficiency
Chu JH, Zang W, Vukmirovic M, Yan X, Adams T, DeIuliis G, Hu B, Mihaljinec A, Schupp JC, Becich MJ, Hochheiser H, Gibson KF, Chen ES, Morris A, Leader JK, Wisniewski SR, Zhang Y, Sciurba FC, Collman RG, Sandhaus R, Herzog EL, Patterson KC, Sauler M, Strange C, Kaminski N. Gene coexpression networks reveal novel molecular endotypes in alpha-1 antitrypsin deficiency. Thorax 2020, 76: 134-143. PMID: 33303696, PMCID: PMC10794043, DOI: 10.1136/thoraxjnl-2019-214301.Peer-Reviewed Original ResearchConceptsWeighted gene co-expression network analysisAlpha-1 antitrypsin deficiencyGene modulesGene co-expression network analysisDifferential gene expression analysisCo-expression network analysisPeripheral blood mononuclear cellsGene expression patternsPBMC gene expression patternsGene coexpression networksAATD individualsGene expression profilesGene expression analysisBronchoalveolar lavageAugmentation therapyClinical variablesAntitrypsin deficiencyGene expression assaysRNA-seqCoexpression networkGene validationExpression analysisExpression assaysWGCNA modulesExpression patternsSingle-Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis.
Schupp JC, Khanal S, Gomez JL, Sauler M, Adams TS, Chupp GL, Yan X, Poli S, Zhao Y, Montgomery RR, Rosas IO, Dela Cruz CS, Bruscia EM, Egan ME, Kaminski N, Britto CJ. Single-Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2020, 202: 1419-1429. PMID: 32603604, PMCID: PMC7667912, DOI: 10.1164/rccm.202004-0991oc.Peer-Reviewed Original ResearchConceptsCF lung diseaseHealthy control subjectsImmune dysfunctionLung diseaseCystic fibrosisControl subjectsSputum cellsAbnormal chloride transportLung mononuclear phagocytesInnate immune dysfunctionDivergent clinical coursesImmune cell repertoireMonocyte-derived macrophagesCF monocytesAirway inflammationClinical courseProinflammatory featuresCell survival programInflammatory responseTissue injuryCell repertoireImmune functionTranscriptional profilesAlveolar macrophagesMononuclear phagocytesA Network of Sputum MicroRNAs is Associated with Neutrophilic Airway Inflammation in Asthma
Gomez JL, Chen A, Diaz MP, Zirn N, Gupta A, Britto C, Sauler M, Yan X, Stewart E, Santerian K, Grant N, Liu Q, Fry R, Rager J, Cohn L, Alexis N, Chupp GL. A Network of Sputum MicroRNAs is Associated with Neutrophilic Airway Inflammation in Asthma. American Journal Of Respiratory And Critical Care Medicine 2020, 0: 51-64. PMID: 32255668, PMCID: PMC7328332, DOI: 10.1164/rccm.201912-2360oc.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulum stressAirway inflammationNeutrophil countClinical featuresT-helper cell type 17Neutrophilic airway inflammationReticulum stressSputum of subjectsLung function impairmentHistory of hospitalizationNumber of neutrophilsPeripheral blood neutrophilsSputum of patientsMicroRNA expressionAsthma severityTh17 pathwayFunction impairmentAirway samplesMicroRNA networkBlood neutrophilsOzone exposureAsthmaSputumCellular sourceClinical phenotypePECAM-1 is Associated WithOutcomes and Response to Treatment in Pulmonary Arterial Hypertension
Clapham KR, Rao Y, Sahay S, Sauler M, Lee PJ, Psotka MA, Fares WH, Ahmad T. PECAM-1 is Associated WithOutcomes and Response to Treatment in Pulmonary Arterial Hypertension. The American Journal Of Cardiology 2020, 127: 198-199. PMID: 32430164, DOI: 10.1016/j.amjcard.2020.04.031.Peer-Reviewed Original ResearchForm, Function, and Dysfunction: Airway Diseases Are Associated With Increased Risk for Rheumatoid Arthritis
Sauler M. Form, Function, and Dysfunction: Airway Diseases Are Associated With Increased Risk for Rheumatoid Arthritis. Arthritis & Rheumatology 2020, 72: 699-701. PMID: 31876099, PMCID: PMC7188593, DOI: 10.1002/art.41193.Commentaries, Editorials and Letters
2016
The clinical significance of the MIF homolog d-dopachrome tautomerase (MIF-2) and its circulating receptor (sCD74) in burn
Kim BS, Stoppe C, Grieb G, Leng L, Sauler M, Assis D, Simons D, Boecker AH, Schulte W, Piecychna M, Hager S, Bernhagen J, Pallua N, Bucala R. The clinical significance of the MIF homolog d-dopachrome tautomerase (MIF-2) and its circulating receptor (sCD74) in burn. Burns 2016, 42: 1265-1276. PMID: 27209369, PMCID: PMC5010466, DOI: 10.1016/j.burns.2016.02.005.Peer-Reviewed Original ResearchConceptsTotal body surface areaMacrophage migration inhibitory factorSerum levelsClinical significanceCytokine macrophage migration inhibitory factorEarly post-burn periodPrediction of sepsisBody surface areaMigration inhibitory factorPost-burn periodBurn severity indexDopachrome tautomeraseClinical outcomesBurn patientsReceptor CD74Healthy controlsBurn injuryEarly predictorMember DPatientsPotential biomarkersCD74Inhibitory factorSoluble CD74Severity Index
2015
Suppression of NLRX1 in chronic obstructive pulmonary disease
Kang MJ, Yoon CM, Kim BH, Lee CM, Zhou Y, Sauler M, Homer R, Dhamija A, Boffa D, West AP, Shadel GS, Ting JP, Tedrow JR, Kaminski N, Kim WJ, Lee CG, Oh YM, Elias JA. Suppression of NLRX1 in chronic obstructive pulmonary disease. Journal Of Clinical Investigation 2015, 125: 2458-2462. PMID: 25938787, PMCID: PMC4497738, DOI: 10.1172/jci71747.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseObstructive pulmonary diseaseCigarette smokeAlveolar destructionPulmonary diseaseHuman chronic obstructive pulmonary diseaseExpression of NLRX1Innate immune pathwaysInnate immune responseQuality of lifeCOPD patientsPulmonary functionSubsequent inflammationImmune responseInflammasome activationMurine modelIndependent cohortImmune pathwaysInflammationDisease severityInflammasome responseImportant mediatorCell apoptosisNLRX1Tissue effects