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 structuresThe 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 ResearchMeSH KeywordsAgedDNA DamageDNA RepairFemaleGene Expression ProfilingHumansImmunohistochemistryLungMaleMiddle AgedPulmonary Disease, Chronic ObstructiveTranscriptomeConceptsDNA 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 samplesCell Death in the Lung: The Apoptosis–Necroptosis Axis
Sauler M, Bazan IS, Lee PJ. Cell Death in the Lung: The Apoptosis–Necroptosis Axis. Annual Review Of Physiology 2018, 81: 1-28. PMID: 30485762, PMCID: PMC6598441, DOI: 10.1146/annurev-physiol-020518-114320.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsApoptosisAsthmaAutophagic Cell DeathHumansIdiopathic Pulmonary FibrosisLung DiseasesNecroptosisPulmonary Arterial HypertensionPulmonary Disease, Chronic ObstructivePyroptosisRegulated Cell DeathRespiratory Distress SyndromeConceptsRegulated cell deathCell deathAutophagic cell deathCell death mechanismsSuperfluous cellsAcute respiratory distress syndromeChronic obstructive pulmonary diseasePulmonary arterial hypertensionIdiopathic pulmonary fibrosisObstructive pulmonary diseaseRespiratory distress syndromeDeath mechanismsCellular mechanismsArterial hypertensionDistress syndromePulmonary diseasePulmonary fibrosisPulmonary disordersMajor mechanismDeathNew modalityPathogenesisNecroptosisMechanismApoptosisA functional macrophage migration inhibitory factor promoter polymorphism is associated with reduced diffusing capacity
Zhang C, Ramsey C, Berical A, Yu L, Leng L, McGinnis K, Song Y, Michael H, McCormack M, Allore H, Morris A, Crothers K, Bucala R, Lee P, Sauler M. A functional macrophage migration inhibitory factor promoter polymorphism is associated with reduced diffusing capacity. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2018, 316: l400-l405. PMID: 30520689, PMCID: PMC6397351, DOI: 10.1152/ajplung.00439.2018.Peer-Reviewed Original ResearchMeSH KeywordsForced Expiratory VolumeGenetic Predisposition to DiseaseLungMacrophage Migration-Inhibitory FactorsPolymorphism, Single NucleotidePromoter Regions, GeneticPulmonary Disease, Chronic ObstructiveRespiratory Function TestsSmokeVital CapacityConceptsMacrophage migration inhibitory factorChronic obstructive pulmonary diseaseMIF -794 CATTAbnormal diffusion capacityCigarette smoke exposureSmoke exposureAssociation of MIFDiffusion capacityMacrophage migration inhibitory factor (MIF) promoter polymorphismsPathogenesis of COPDChronic cigarette smoke exposureMultivariable logistic regression modelModifiable risk factorsObstructive pulmonary diseaseMigration inhibitory factorCross-sectional analysisLogistic regression modelsCommon genetic polymorphismsInnate immune genesAirflow obstructionMIF expressionCOPD severityPulmonary diseaseMIF allelesRisk factors
2024
COPD-iNET: a call to the lung community for action to combat the global epidemic of COPD.
Yildirim A, Conlon T, Adcock I, Gosens R, Lehmann M, Kapellos T, Tesfaigzi Y, Polverino F, Sauler M, Wasnick R, Neptune E. COPD-iNET: a call to the lung community for action to combat the global epidemic of COPD. European Respiratory Journal 2024, 64: 2400921. PMID: 39326903, DOI: 10.1183/13993003.00921-2024.Peer-Reviewed Original ResearchSpatial Transcriptomics Resolve an Emphysema-Specific Lymphoid Follicle B Cell Signature in Chronic Obstructive Pulmonary Disease
Rojas-Quintero J, Ochsner S, New F, Divakar P, Yang C, Wu T, Robinson J, Chandrashekar D, Banovich N, Rosas I, Sauler M, Kheradmand F, Gaggar A, Margaroli C, San Jose Estepar R, McKenna N, Polverino F. Spatial Transcriptomics Resolve an Emphysema-Specific Lymphoid Follicle B Cell Signature in Chronic Obstructive Pulmonary Disease. American Journal Of Respiratory And Critical Care Medicine 2024, 209: 48-58. PMID: 37934672, PMCID: PMC10870877, DOI: 10.1164/rccm.202303-0507le.Peer-Reviewed Original ResearchMeSH KeywordsEmphysemaGene Expression ProfilingHumansLymphadenopathyProteomicsPulmonary Disease, Chronic ObstructivePulmonary EmphysemaConceptsChronic obstructive pulmonary diseaseB cell activationObstructive pulmonary diseaseLymphoid folliclesCell activationPulmonary diseaseGOLD 1Chronic Obstructive Lung Disease (GOLD) 1Chronic B-cell activationB cell signaturesDegree of emphysemaB cell marker genesB cell maturationSevere emphysemaAntiinflammatory profileEmphysema measurementsTomographic scanLung sectionsAntigen presentationGOLD 3Centrilobular emphysemaImmune componentsEmphysema pathogenesisEmphysemaLung samples
2023
Alveolar type II epithelial cell FASN maintains lipid homeostasis in experimental COPD
Fan L, McConn K, Plataki M, Kenny S, Williams N, Kim K, Quirke J, Chen Y, Sauler M, Möbius M, Chung K, Gomez E, Choi A, Xu J, Cloonan S. Alveolar type II epithelial cell FASN maintains lipid homeostasis in experimental COPD. JCI Insight 2023, 8: e163403. PMID: 37606038, PMCID: PMC10543729, DOI: 10.1172/jci.insight.163403.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEpithelial CellsFatty Acid Synthase, Type IIFatty Acid SynthasesHomeostasisLipidsMicePulmonary Disease, Chronic ObstructivePulmonary SurfactantsSurface-Active AgentsConceptsChronic obstructive pulmonary diseaseAEC2 cellsFatty acid synthaseCigarette smokeExperimental chronic obstructive pulmonary diseaseBronchoalveolar lavage fluid neutrophilsLipid metabolismDisease-chronic obstructive pulmonary diseaseObstructive pulmonary diseaseAlveolar epithelial type II cellsEpithelial type II cellsType II cellsCOPD developmentPulmonary diseaseAirspace enlargementBALF proteinLipogenesis enzymesFerroptosis markersHigh-throughput lipidomic analysisSurfactant phospholipidsMiceSurfactant synthesisLipid homeostasisII cellsCell functionA 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 ResearchMeSH KeywordsBreast NeoplasmsFemaleGene Expression ProfilingGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansLungPolymorphism, Single NucleotidePulmonary Disease, Chronic ObstructiveConceptsCell 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 cancerTaking Small Airways in Chronic Obstructive Pulmonary Disease to TASC
Sauler M, Hackett T. Taking Small Airways in Chronic Obstructive Pulmonary Disease to TASC. American Journal Of Respiratory And Critical Care Medicine 2023, 207: 1114-1115. PMID: 36821491, PMCID: PMC10161754, DOI: 10.1164/rccm.202302-0295ed.Peer-Reviewed Original Research
2022
Lung Spatial Profiling Reveals a T Cell Signature in COPD Patients with Fatal SARS-CoV-2 Infection
Yang CX, Tomchaney M, Landecho MF, Zamacona BR, Oto M, Zulueta J, Malo J, Knoper S, Contoli M, Papi A, Vasilescu DM, Sauler M, Straub C, Tan C, Martinez FD, Bhattacharya D, Rosas IO, Kheradmand F, Hackett TL, Polverino F. Lung Spatial Profiling Reveals a T Cell Signature in COPD Patients with Fatal SARS-CoV-2 Infection. Cells 2022, 11: 1864. PMID: 35740993, PMCID: PMC9220844, DOI: 10.3390/cells11121864.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseCOPD patientsLung parenchymaFatal SARS-CoV-2 infectionsMemory CD4 T cell responsesPre-existing lung diseaseCD4 T cell responsesSARS-CoV-2 infectionSARS-CoV-2 entryMemory T cell differentiationSARS-CoV-2 disease 2019Obstructive pulmonary diseaseT cell responsesT-cell signatureCOVID-19 infectionCOVID-19T cell differentiationAntigen primingMemory CD4Pulmonary diseaseControl lungsImmune microenvironmentLung diseaseT cellsT lymphocytesCharacterization of pulmonary vascular remodeling and MicroRNA-126-targets in COPD-pulmonary hypertension
Goel K, Egersdorf N, Gill A, Cao D, Collum S, Jyothula S, Huang H, Sauler M, Lee P, Majka S, Karmouty-Quintana H, Petrache I. Characterization of pulmonary vascular remodeling and MicroRNA-126-targets in COPD-pulmonary hypertension. Respiratory Research 2022, 23: 349. PMID: 36522710, PMCID: PMC9756782, DOI: 10.1186/s12931-022-02267-4.Peer-Reviewed Original ResearchMeSH KeywordsADAM ProteinsCeramidesEndothelial CellsHumansHypertension, PulmonaryLungMembrane ProteinsMicroRNAsPulmonary ArteryPulmonary Disease, Chronic ObstructiveVascular RemodelingConceptsSmall pulmonary arteriesChronic cigarette smokingPulmonary vascular remodelingPulmonary hypertensionPulmonary arteryLung microvasculatureVascular remodelingEndothelial cellsCOPD-PHMiR126 expressionChronic obstructive pulmonary disease patientsObstructive pulmonary disease patientsCOPD pulmonary hypertensionPulmonary artery sizePulmonary artery remodelingPulmonary disease patientsPulmonary vascular bedPulmonary arterial wallEndothelial cell marker CD31Microvascular endothelial cellsEndothelial cell markersVessel endothelial cellsNon-COPD lungsLarge vessel endothelial cellsArtery remodeling
2021
Metformin: 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 ResearchMeSH KeywordsAgedAged, 80 and overAnimalsBiomarkersCigarette SmokingDisease ProgressionFemaleFollow-Up StudiesHumansMaleMetforminMiceMice, Inbred C57BLMiddle AgedProtective AgentsPulmonary Disease, Chronic ObstructivePulmonary EmphysemaTreatment OutcomeConceptsChronic 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 effects
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 ResearchMeSH KeywordsAdultAlpha 1-Antitrypsin DeficiencyBronchoalveolar Lavage FluidFemaleGene Expression ProfilingGene Regulatory NetworksGenotypeHumansMaleMiddle AgedNeutrophilsProspective StudiesPulmonary Disease, Chronic ObstructiveTranscriptomeConceptsWeighted 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 patternsForm, 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 LettersMeSH KeywordsArthritis, RheumatoidAsthmaFemaleHumansProspective StudiesPulmonary Disease, Chronic Obstructive
2015
Role of macrophage migration inhibitory factor in age-related lung disease
Sauler M, Bucala R, Lee PJ. Role of macrophage migration inhibitory factor in age-related lung disease. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2015, 309: l1-l10. PMID: 25957294, PMCID: PMC4491511, DOI: 10.1152/ajplung.00339.2014.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAgingAnimalsCytokinesHumansInflammationIntramolecular OxidoreductasesLung NeoplasmsMacrophage Migration-Inhibitory FactorsMicePneumonia, BacterialPulmonary Disease, Chronic ObstructiveConceptsMacrophage migration inhibitory factorAge-related lung diseaseMigration inhibitory factorLung diseaseInhibitory factorChronic obstructive lung diseaseChronic lung diseaseObstructive lung diseaseCommon respiratory disorderPulmonary fibrosisClinical manifestationsProinflammatory cytokinesLung cancerRespiratory disordersImmune systemVariant allelesDiseaseHost factorsSuch diseasesPotent upstream regulatorUpstream regulatorPneumoniaFibrosisBody of literatureCytokinesSuppression 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