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 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 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 StatementsConceptsRegulated 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 ResearchConceptsMacrophage 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
Spatial 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 ResearchConceptsChronic 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
Spatial Transcriptomics Resolve an Emphysema-specific Lymphoid Follicle B Cell Signature in COPD.
Rojas-Quintero J, Ochsner S, New F, Divakar P, Yang C, Wu T, Robinson J, Shimoga 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 COPD. American Journal Of Respiratory And Critical Care Medicine 2023 PMID: 38064378, DOI: 10.1164/rccm.202303-0507oc.Peer-Reviewed Original ResearchChronic obstructive pulmonary diseaseB cell activationLymphoid folliclesCOPD patientsGOLD 1Cell activationChronic B-cell activationObstructive pulmonary diseaseB cell signaturesAnti-inflammatory profileChest CT scanDegree of emphysemaB cell marker genesB cell maturationSevere emphysemaPulmonary diseaseEmphysema measurementsLung sectionsAntigen presentationGOLD 3Centrilobular emphysemaCT scanImmune componentsEmphysema pathogenesisEmphysemaAlveolar 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 ResearchConceptsChronic 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 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
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 lymphocytes
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 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 effects
2020
Non-coding RNAs as Regulators of Cellular Senescence in Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease
Omote N, Sauler M. Non-coding RNAs as Regulators of Cellular Senescence in Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease. Frontiers In Medicine 2020, 7: 603047. PMID: 33425948, PMCID: PMC7785852, DOI: 10.3389/fmed.2020.603047.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsNon-coding RNAsCellular stress responseNon-coding RNACellular senescenceCell fateChronic obstructive pulmonary diseaseStress responseAlternative cell fatesIdiopathic pulmonary fibrosisLong non-coding RNAsObstructive pulmonary diseaseCellular stressorsCellular stressKey regulatorSenescencePulmonary diseaseDNA damagePulmonary fibrosisMitochondrial dysfunctionRNACellular mechanismsChronic lung diseasePotential therapeutic roleRegulatorOxidative stress
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
2014
Oxidants in Acute and Chronic Lung Disease
Mannam P, Srivastava A, Sugunaraj JP, Lee PJ, Sauler M. Oxidants in Acute and Chronic Lung Disease. Journal Of Blood & Lymph 2014, 4: 1000128. PMID: 25705575, PMCID: PMC4335304, DOI: 10.4172/2165-7831.1000128.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsChronic obstructive pulmonary diseaseAcute lung injuryLung diseaseChronic lung diseaseObstructive pulmonary diseaseReactive oxygen speciesAnti-oxidant strategiesLung injuryPulmonary diseaseLung pathologyOxidant responsesConsistent benefitHomeostatic functionsBeneficial effectsAdverse effectsOxidant generationDiseaseBeneficial resultsOxygen speciesAcuteInjuryTherapyPathologyNovel areaImportant role