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 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
Molecular Characterization of the Distal Lung: Novel Insights from Chronic Obstructive Pulmonary Disease Omics.
Castaldi P, Sauler M. Molecular Characterization of the Distal Lung: Novel Insights from Chronic Obstructive Pulmonary Disease Omics. American Journal Of Respiratory And Critical Care Medicine 2024, 210: 147-154. PMID: 38701385, PMCID: PMC11273319, DOI: 10.1164/rccm.202310-1972pp.Peer-Reviewed Original ResearchLung Transcriptomics Links Emphysema to Barrier Dysfunction and Macrophage Subpopulations.
Lu R, Gregory A, Suryadevara R, Xu Z, Jain D, Morrow J, Hobbs B, Yun J, Lichtblau N, Chase R, Curtis J, Sauler M, Bartholmai B, Silverman E, Hersh C, Castaldi P, Boueiz A. Lung Transcriptomics Links Emphysema to Barrier Dysfunction and Macrophage Subpopulations. American Journal Of Respiratory And Critical Care Medicine 2024 PMID: 38935868, DOI: 10.1164/rccm.202305-0793oc.Peer-Reviewed Original ResearchRNA sequencing dataAlternative splicingExpressed genesFunctional pathwaysCell typesBiological pathwaysGene expressionTranscriptomic featuresGene regulatory processesDysregulated pathwaysSingle-cell RNA sequencing dataRNA-seq analysisLung cell typesLung Tissue Research ConsortiumTranscriptome analysisGenesCell-typeDifferential expressionMultiple lung cell typesPathway activationTranscriptomic signaturesPathway dysregulationRegulatory processesSplicingPathwayEpidermal Growth Factor Receptor Regulates Beclin-1 in Hyperoxia-Induced Lung Injury
Harris Z, Sun Y, Korde A, Hu B, Sharma L, Manning E, Joerns J, Clark B, Stanley G, Shin H, Placek L, Unutmaz D, Chun H, Sauler M, Rajagopalan G, Zhang X, Wang H, Kang M, Koff J. Epidermal Growth Factor Receptor Regulates Beclin-1 in Hyperoxia-Induced Lung Injury. 2024, a6841-a6841. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a6841.Peer-Reviewed Original ResearchAlveolar Type 2 Cells With Impaired Proteostasis Signal to Monocyte-derived Macrophages Via a MIF/DDT-CD74 Signaling Network to Promotes Pulmonary Fibrosis in IPF
Kim S, Nouws J, Cooley J, Ahangari F, Leng L, Elias J, Kaminski N, Lee P, Redente E, Kang M, Sun H, Herzog E, Bucala R, Prasse A, Sauler M. Alveolar Type 2 Cells With Impaired Proteostasis Signal to Monocyte-derived Macrophages Via a MIF/DDT-CD74 Signaling Network to Promotes Pulmonary Fibrosis in IPF. 2024, a3001-a3001. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a3001.Peer-Reviewed Original ResearchCFTR Modulators Reprogram Sex-Specific Airway Neutrophil Signaling
Yin H, Kockar Kizilirmak T, Li N, Adams T, Sauler M, Gomez J, Britto-Leon C. CFTR Modulators Reprogram Sex-Specific Airway Neutrophil Signaling. 2024, a7454-a7454. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a7454.Peer-Reviewed Original ResearchRole of Noradrenaline and Macrophage Dynamics in Pulmonary Fibrosis
Ishikawa G, Peng X, Mcgovern J, Ghincea A, Saber T, Sun H, Sauler M, Ryu C, Herzog E. Role of Noradrenaline and Macrophage Dynamics in Pulmonary Fibrosis. 2024, a5206-a5206. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a5206.Peer-Reviewed Original ResearchReduced Epithelial NUPR1 Negatively Impacts Mitochondrial Function and Metabolism, and Increases Susceptibility to Emphysema
Nouws J, Yang T, Santofimia-Castaño P, Iovanna J, Sauler M. Reduced Epithelial NUPR1 Negatively Impacts Mitochondrial Function and Metabolism, and Increases Susceptibility to Emphysema. 2024, a2620-a2620. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a2620.Peer-Reviewed Original ResearchParaseptal Emphysema Is Characterized by a TLR-Th17-driven Adaptive Immune Response
Rojas-Quintero J, Ochsner S, Sauler M, Mckenna N, San Jose Estepar R, Polverino F. Paraseptal Emphysema Is Characterized by a TLR-Th17-driven Adaptive Immune Response. 2024, a1041-a1041. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a1041.Peer-Reviewed Original ResearchStem cell migration drives lung repair in living mice
Chioccioli M, Liu S, Magruder S, Tata A, Borriello L, McDonough J, Konkimalla A, Kim S, Nouws J, Gonzalez D, Traub B, Ye X, Yang T, Entenberg D, Krishnaswamy S, Hendry C, Kaminski N, Tata P, Sauler M. Stem cell migration drives lung repair in living mice. Developmental Cell 2024, 59: 830-840.e4. PMID: 38377991, PMCID: PMC11003834, DOI: 10.1016/j.devcel.2024.02.003.Peer-Reviewed Original ResearchStem cell migrationCell migrationAlveolar type 2 cellsAlveolar unitsStem cell motilityAlveolar type 1 cellsStem cell activityCellular response to injuryResponse to injuryType 2 cellsMotile phenotypeType 1 cellsCell motilityLung repairImpaired regenerationGenetic depletionCell activationAT2Stem cellsTissue repairAT1Longitudinal imagingInjuryMotilityCellular resolutionSpatial 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 pathogenesisEmphysemaCigarette Smoking and the Airway Epithelium: Characterizing Changes in Gene Expression over Time
Castaldi P, Sauler M. Cigarette Smoking and the Airway Epithelium: Characterizing Changes in Gene Expression over Time. American Journal Of Respiratory And Critical Care Medicine 2023, 208: 749-750. PMID: 37610776, PMCID: PMC10563183, DOI: 10.1164/rccm.202308-1371ed.Peer-Reviewed Original ResearchAlveolar 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 function