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 samplesA 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
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 cancerVISTA (PD-1H) Is a Crucial Immune Regulator to Limit Pulmonary Fibrosis.
Kim S, Adams T, Hu Q, Shin H, Chae G, Lee S, Sharma L, Kwon H, Lee F, Park H, Huh W, Manning E, Kaminski N, Sauler M, Chen L, Song J, Kim T, Kang M. VISTA (PD-1H) Is a Crucial Immune Regulator to Limit Pulmonary Fibrosis. American Journal Of Respiratory Cell And Molecular Biology 2023, 69: 22-33. PMID: 36450109, PMCID: PMC10324045, DOI: 10.1165/rcmb.2022-0219oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisImmune regulatorsTherapeutic potentialHuman idiopathic pulmonary fibrosisCrucial immune regulatorsNovel immune regulatorPulmonary fibrosis micePulmonary fibrosis modelNovel therapeutic targetRole of VISTAWild-type littermatesMonocyte-derived macrophagesT lymphocyte lineageVISTA expressionIPF treatmentAntibody treatmentImmune landscapeFibrotic mediatorsLung fibrosisFibrosis miceInflammatory responseFibrosis modelMyeloid populationsTherapeutic target
2022
A lung targeted miR-29 mimic as a therapy for pulmonary fibrosis
Chioccioli M, Roy S, Newell R, Pestano L, Dickinson B, Rigby K, Herazo-Maya J, Jenkins G, Ian S, Saini G, Johnson SR, Braybrooke R, Yu G, Sauler M, Ahangari F, Ding S, DeIuliis J, Aurelien N, Montgomery RL, Kaminski N. A lung targeted miR-29 mimic as a therapy for pulmonary fibrosis. EBioMedicine 2022, 85: 104304. PMID: 36265417, PMCID: PMC9587275, DOI: 10.1016/j.ebiom.2022.104304.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisNon-human primatesPulmonary fibrosisAnimal modelsPro-fibrotic genesAnti-fibrotic efficacyMiR-29 mimicsHuman peripheral bloodMiR-29b levelsHuman lung fibroblastsIPF patientsIPF diagnosisPeripheral bloodReduced fibrosisAdverse findingsPotential therapyLung slicesTGF-β1Relevant dosesLung fibroblastsNIH-NHLBIFibrosisTherapyCollagen productionProfibrotic gene programEpidermal Growth Factor Receptor Inhibition Is Protective in Hyperoxia‐Induced Lung Injury
Harris ZM, Sun Y, Joerns J, Clark B, Hu B, Korde A, Sharma L, Shin HJ, Manning EP, Placek L, Unutmaz D, Stanley G, Chun H, Sauler M, Rajagopalan G, Zhang X, Kang MJ, Koff JL. Epidermal Growth Factor Receptor Inhibition Is Protective in Hyperoxia‐Induced Lung Injury. Oxidative Medicine And Cellular Longevity 2022, 2022: 9518592. PMID: 36193076, PMCID: PMC9526641, DOI: 10.1155/2022/9518592.Peer-Reviewed Original ResearchConceptsAcute lung injuryEpidermal growth factor receptorAlveolar epithelial cellsLung injurySevere hyperoxiaEGFR inhibitionEpithelial cellsHyperoxia-Induced Lung InjuryRole of EGFRMurine alveolar epithelial cellsGrowth factor receptor inhibitionWorse clinical outcomesEpidermal growth factor receptor inhibitionHuman alveolar epithelial cellsWild-type littermatesPoly (ADP-ribose) polymeraseTerminal dUTP nickGrowth factor receptorClinical outcomesImproved survivalReceptor inhibitionLung repairProtective roleComplex roleEGFR deletionLung 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 ResearchConceptsSmall 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
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 populationsSPLUNC1: a novel marker of cystic fibrosis exacerbations
Khanal S, Webster M, Niu N, Zielonka J, Nunez M, Chupp G, Slade MD, Cohn L, Sauler M, Gomez JL, Tarran R, Sharma L, Dela Cruz CS, Egan M, Laguna T, Britto CJ. SPLUNC1: a novel marker of cystic fibrosis exacerbations. European Respiratory Journal 2021, 58: 2000507. PMID: 33958427, PMCID: PMC8571118, DOI: 10.1183/13993003.00507-2020.Peer-Reviewed Original ResearchConceptsAcute pulmonary exacerbationsSPLUNC1 levelsCystic fibrosisClinical outcomesCF participantsLong-term disease controlNasal epithelium clone 1Cystic fibrosis exacerbationsHigher AE riskLung function declineCytokines interleukin-1βTumor necrosis factorAE riskClinical worseningPulmonary exacerbationsStable patientsLung functionAirway clearanceFunction declineSputum collectionAcute inflammationInflammatory cytokinesMicrobiology findingsCF careClinical management
2019
Endothelial toll‐like receptor 4 maintains lung integrity via epigenetic suppression of p16INK4a
Kim S, Shan P, Hwangbo C, Zhang Y, Min J, Zhang X, Ardito T, Li A, Peng T, Sauler M, Lee PJ. Endothelial toll‐like receptor 4 maintains lung integrity via epigenetic suppression of p16INK4a. Aging Cell 2019, 18: e12914. PMID: 30790400, PMCID: PMC6516428, DOI: 10.1111/acel.12914.Peer-Reviewed Original ResearchConceptsToll-like receptor 4Senescence-related gene expressionLung integritySenescence-associated genesReceptor 4New functional roleLung ECsInnate immune receptor toll-like receptor 4Immune receptor toll-like receptor 4Role of TLR4Endothelial Toll-like receptor 4Receptor Toll-like receptor 4Epigenetic regulationHistone H4Epigenetic suppressionTLR4-/- miceGene expressionEndogenous p16Molecular mechanismsWild-type miceNovel roleExpression of p16Lung endothelial cellsFunctional roleDistinct roles
2018
BPIFA1 regulates lung neutrophil recruitment and interferon signaling during acute inflammation
Britto CJ, Niu N, Khanal S, Huleihel L, Herazo-Maya J, Thompson A, Sauler M, Slade MD, Sharma L, Dela Cruz CS, Kaminski N, Cohn LE. BPIFA1 regulates lung neutrophil recruitment and interferon signaling during acute inflammation. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2018, 316: l321-l333. PMID: 30461288, PMCID: PMC6397348, DOI: 10.1152/ajplung.00056.2018.Peer-Reviewed Original ResearchConceptsLung inflammationAcute inflammationC motif chemokine ligand 10Lung neutrophil recruitmentRegulation of CXCL10Acute lung inflammationBronchoalveolar lavage concentrationsChemokine ligand 10Innate immune responseIFN regulatory factorIntranasal LPSLavage concentrationsLung recruitmentNeutrophil recruitmentWT miceImmune effectsLung diseasePMN recruitmentInflammatory responseLPS treatmentLung tissueInflammatory signalsImmune responseImmunomodulatory propertiesInflammation
2014
Endothelial PINK1 Mediates the Protective Effects of NLRP3 Deficiency during Lethal Oxidant Injury
Zhang Y, Sauler M, Shinn AS, Gong H, Haslip M, Shan P, Mannam P, Lee PJ. Endothelial PINK1 Mediates the Protective Effects of NLRP3 Deficiency during Lethal Oxidant Injury. The Journal Of Immunology 2014, 192: 5296-5304. PMID: 24778451, PMCID: PMC4047670, DOI: 10.4049/jimmunol.1400653.Peer-Reviewed Original ResearchConceptsAcute respiratory failurePTEN-induced putative kinase 1Respiratory failureWild-type miceNLRP3 deficiencyAutophagy/mitophagySpecific therapyProtective effectProtein NLRP3Oxidant injuryLung endotheliumHigh mortalityHyperoxiaGenetic deletionHigher basalIntermediate susceptibilityMiceOxidant generationPutative kinase 1PINK1 expressionProteasome activationNovel roleDouble knockoutEndotheliumKinase 1
2013
Lung endothelial HO‐1 targeting in vivo using lentiviral miRNA regulates apoptosis and autophagy during oxidant injury
Zhang Y, Jiang G, Sauler M, Lee PJ. Lung endothelial HO‐1 targeting in vivo using lentiviral miRNA regulates apoptosis and autophagy during oxidant injury. The FASEB Journal 2013, 27: 4041-4058. PMID: 23771928, PMCID: PMC4046184, DOI: 10.1096/fj.13-231225.Peer-Reviewed Original ResearchConceptsEndothelial HO-1Murine lung endothelial cellsHO-1Lung endotheliumHeme oxygenase-1 inductionHO-1 knockdownLung endothelial cellsOxygenase-1 inductionLung cell typesLung injuryWT miceMultiple lung cell typesVascular endothelium cadherinOxidant injuryCrucial defense mechanismHyperoxiaEndothelial cellsOxidative stressOxidant challengeEndotheliumMajor targetROS generationInjuryLentiviral vectorsVivo