Featured Publications
The 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 profilesCharacterization 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
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 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
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
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 macrophagesIntegrated 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 populationsSingle-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 patterns