2021
Transcriptomics of bronchoalveolar lavage cells identifies new molecular endotypes of sarcoidosis
Vukmirovic M, Yan X, Gibson KF, Gulati M, Schupp JC, DeIuliis G, Adams TS, Hu B, Mihaljinec A, Woolard TN, Lynn H, Emeagwali N, Herzog EL, Chen ES, Morris A, Leader JK, Zhang Y, Garcia JGN, Maier LA, Collman RG, Drake WP, Becich MJ, Hochheiser H, Wisniewski SR, Benos PV, Moller DR, Prasse A, Koth LL, Kaminski N. Transcriptomics of bronchoalveolar lavage cells identifies new molecular endotypes of sarcoidosis. European Respiratory Journal 2021, 58: 2002950. PMID: 34083402, PMCID: PMC9759791, DOI: 10.1183/13993003.02950-2020.Peer-Reviewed Original ResearchMeSH KeywordsBronchoalveolar LavageBronchoalveolar Lavage FluidHumansSarcoidosisSarcoidosis, PulmonaryTranscriptomeConceptsWeighted gene co-expression network analysisGene co-expression network analysisCo-expression network analysisGene expression programsGene expression patternsDistinct transcriptional programsImmune response pathwaysIon Torrent ProtonMicroarray expression datasetsExpression programsTranscriptional programsPhenotypic traitsGene modulesResponse pathwaysRNA sequencingMolecular endotypesExpression patternsGene expressionHilar lymphadenopathyOrgan involvementGenomic researchMechanistic targetExpression datasetsT helper type 1T cell immune responsesElevated IL-15 concentrations in the sarcoidosis lung are independent of granuloma burden and disease phenotypes
Minasyan M, Sharma L, Pivarnik T, Liu W, Adams T, Bermejo S, Peng X, Liu A, Ishikawa G, Perry C, Kaminski N, Gulati M, Herzog EL, Dela Cruz CS, Ryu C. Elevated IL-15 concentrations in the sarcoidosis lung are independent of granuloma burden and disease phenotypes. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2021, 320: l1137-l1146. PMID: 33851886, PMCID: PMC8285626, DOI: 10.1152/ajplung.00575.2020.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBronchoalveolar Lavage FluidDisease Models, AnimalGranulomaInflammationInterleukin-15LungPhenotypeSarcoidosisSarcoidosis, PulmonaryConceptsIL-15 concentrationsIL-15Bronchoalveolar lavageDisease pathogenesisSarcoidosis lungClinical manifestationsLineages of miceIL-15 receptor αHuman cohortsInflammation of sarcoidosisIL-15 levelsOngoing inflammatory processSystemic granulomatous diseaseNumber of granulomasDisease phenotypeSarcoidosis cohortTDM administrationGranuloma numberComorbid conditionsClinical progressionInterleukin-15Granulomatous diseaseInflammatory processGranuloma formationHealthy controls
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 patternsCathepsin B promotes collagen biosynthesis, which drives bronchiolitis obliterans syndrome
Morrone C, Smirnova NF, Jeridi A, Kneidinger N, Hollauer C, Schupp JC, Kaminski N, Jenne D, Eickelberg O, Yildirim AÖ. Cathepsin B promotes collagen biosynthesis, which drives bronchiolitis obliterans syndrome. European Respiratory Journal 2020, 57: 2001416. PMID: 33303550, DOI: 10.1183/13993003.01416-2020.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBronchiolitis ObliteransBronchoalveolar Lavage FluidCathepsin BHumansLungLung TransplantationMiceConceptsBronchoalveolar lavage fluidCathepsin B activityHealthy donorsLung tissueCollagen depositionB activityCathepsin BBronchiolitis obliterans syndromeProgression of BOSFluorescence resonance energy transfer-based assayPromising therapeutic targetGrowth factor-β1Cathepsin B levelsSubsequent collagen depositionBOS pathogenesisBOS patientsBOS progressionLTx patientsLymphocytic bronchiolitisObliterans syndromeLung transplantationPeribronchial fibrosisPulmonary dysfunctionLung functionMajor complicationsExpression of SARS-CoV-2 receptor ACE2 and coincident host response signature varies by asthma inflammatory phenotype
Camiolo M, Gauthier M, Kaminski N, Ray A, Wenzel SE. Expression of SARS-CoV-2 receptor ACE2 and coincident host response signature varies by asthma inflammatory phenotype. Journal Of Allergy And Clinical Immunology 2020, 146: 315-324.e7. PMID: 32531372, PMCID: PMC7283064, DOI: 10.1016/j.jaci.2020.05.051.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAngiotensin-Converting Enzyme 2AsthmaBetacoronavirusBiomarkersBronchiBronchoalveolar Lavage FluidCohort StudiesCoronavirus InfectionsCOVID-19EosinophilsFemaleGene Expression ProfilingHumansInterferon Type IInterferon-gammaMaleMiddle AgedPandemicsPeptidyl-Dipeptidase APneumonia, ViralProtein Interaction MappingReceptors, VirusRisk FactorsSARS-CoV-2Severity of Illness IndexT-LymphocytesTranscriptomeUnited StatesConceptsCoronavirus disease 2019Severe coronavirus disease 2019Subset of patientsDisease 2019Risk factorsBronchial epitheliumAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSevere acute respiratory syndrome coronavirus 2Syndrome coronavirus 2 infectionType 2 inflammatory biomarkersAcute respiratory syndrome coronavirus 2Receptor ACE2SARS-CoV-2 receptor ACE2Respiratory syndrome coronavirus 2Asthma inflammatory phenotypesLarge asthma cohortsLower peripheral bloodT cell-activating factorCoronavirus 2 infectionEnzyme 2 (ACE2) expressionHistory of hypertensionDiagnosis of asthmaBronchoalveolar lavage lymphocytesT cell recruitment
2019
BAL Cell Gene Expression in Severe Asthma Reveals Mechanisms of Severe Disease and Influences of Medications
Weathington N, O’Brien M, Radder J, Whisenant TC, Bleecker ER, Busse WW, Erzurum SC, Gaston B, Hastie A, Jarjour N, Meyers D, Milosevic J, Moore W, Tedrow J, Trudeau J, Wong H, Wu W, Kaminski N, Wenzel S, Modena B. BAL Cell Gene Expression in Severe Asthma Reveals Mechanisms of Severe Disease and Influences of Medications. American Journal Of Respiratory And Critical Care Medicine 2019, 200: 837-856. PMID: 31161938, PMCID: PMC6812436, DOI: 10.1164/rccm.201811-2221oc.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic beta-AgonistsAdultAsthmaBronchoalveolar Lavage FluidCase-Control StudiesCyclic AMPEosinophilsEpithelial CellsFemaleGene ExpressionHumansIn Vitro TechniquesLymphocytesMacrophages, AlveolarMaleNeutrophilsSequence Analysis, RNASeverity of Illness IndexSignal TransductionTHP-1 CellsConceptsCell gene expressionGene expressionAirway epithelial cell gene expressionEpithelial cell gene expressionGlobal gene expressionCellular gene expressionCell expression profilesAsthma susceptibility lociProtein levelsSystem-wide analysisExpression networksImportant disease mechanismCoexpression networkCellular milieuExpression changesExpression profilesSusceptibility lociCellular modelDisease mechanismsBiomolecular mechanismsNew targetsRobust upregulationSample traitsGenesExpressionPlasma mitochondrial DNA is associated with extrapulmonary sarcoidosis
Ryu C, Brandsdorfer C, Adams T, Hu B, Kelleher DW, Yaggi M, Manning EP, Walia A, Reeves B, Pan H, Winkler J, Minasyan M, Dela Cruz CS, Kaminski N, Gulati M, Herzog EL. Plasma mitochondrial DNA is associated with extrapulmonary sarcoidosis. European Respiratory Journal 2019, 54: 1801762. PMID: 31273041, PMCID: PMC8088542, DOI: 10.1183/13993003.01762-2018.Peer-Reviewed Original ResearchConceptsExtrapulmonary diseaseMitochondrial DNAExtracellular mtDNABAL fluidAlpha-1 antitrypsin deficiencyPlasma mitochondrial DNAPlasma of patientsAfrican AmericansExtrapulmonary sarcoidosisSarcoidosis cohortSarcoidosis subjectsScadding stageAfrican American descentClinical featuresClinical findingsGranulomatous diseaseHealthy controlsAntitrypsin deficiencyGenomic researchHigher oddsSarcoidosisAggressive phenotypeMechanistic basisDiseaseTherapeutic insightsBAL Cell Gene Expression Is Indicative of Outcome and Airway Basal Cell Involvement in Idiopathic Pulmonary Fibrosis
Prasse A, Binder H, Schupp JC, Kayser G, Bargagli E, Jaeger B, Hess M, Rittinghausen S, Vuga L, Lynn H, Violette S, Jung B, Quast K, Vanaudenaerde B, Xu Y, Hohlfeld JM, Krug N, Herazo-Maya JD, Rottoli P, Wuyts WA, Kaminski N. BAL Cell Gene Expression Is Indicative of Outcome and Airway Basal Cell Involvement in Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2019, 199: 622-630. PMID: 30141961, PMCID: PMC6396865, DOI: 10.1164/rccm.201712-2551oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisAirway basal cellsChronic obstructive pulmonary diseaseObstructive pulmonary diseasePulmonary diseaseBAL cellsBasal cellsPulmonary fibrosisControl subjectsCell gene expressionIndependent IPF cohortsNine-gene signatureIPF cohortDerivation cohortClinical parametersRetrospective studyUnivariate analysisUnpredictable courseCell involvementDiscovery cohortGene expressionHealthy volunteersCox modelStage IIIFatal disease
2016
Expression of asthma susceptibility genes in bronchial epithelial cells and bronchial alveolar lavage in the Severe Asthma Research Program (SARP) cohort
Li X, Hawkins GA, Moore WC, Hastie AT, Ampleford EJ, Milosevic J, Li H, Busse WW, Erzurum SC, Kaminski N, Wenzel SE, Bleecker ER, Meyers DA. Expression of asthma susceptibility genes in bronchial epithelial cells and bronchial alveolar lavage in the Severe Asthma Research Program (SARP) cohort. Journal Of Asthma 2016, 53: 775-782. PMID: 27050946, PMCID: PMC5137190, DOI: 10.3109/02770903.2016.1158268.Peer-Reviewed Original Research
2015
eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS‐identified asthma genes
Li X, Hastie AT, Hawkins GA, Moore WC, Ampleford EJ, Milosevic J, Li H, Busse WW, Erzurum SC, Kaminski N, Wenzel SE, Meyers DA, Bleecker ER. eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS‐identified asthma genes. Allergy 2015, 70: 1309-1318. PMID: 26119467, PMCID: PMC4583797, DOI: 10.1111/all.12683.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAsthmaBronchoalveolar Lavage FluidCase-Control StudiesChromosome MappingEpithelial CellsFemaleGenetic Association StudiesGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansImmunoglobulin EMaleOrgan SpecificityPolymorphism, Single NucleotideQuantitative Trait LociRespiratory Function TestsRespiratory MucosaConceptsExpression quantitative trait lociGenome-wide association studiesSingle nucleotide polymorphismsAsthma genesQuantitative trait lociGenes/single-nucleotide polymorphismsCis-eQTL analysisFurther functional studiesDisease-relevant tissuesDecreased expressionTrait lociCausal genesTranscription analysisGene expressionPromoter regionAsthma-related genesAssociation studiesBronchial epithelial cellsProtein secretionGenesFunctional studiesNucleotide polymorphismsSpecific regulationExpression levelsExpression of IL33
2008
MMP1 and MMP7 as Potential Peripheral Blood Biomarkers in Idiopathic Pulmonary Fibrosis
Rosas IO, Richards TJ, Konishi K, Zhang Y, Gibson K, Lokshin AE, Lindell KO, Cisneros J, MacDonald SD, Pardo A, Sciurba F, Dauber J, Selman M, Gochuico BR, Kaminski N. MMP1 and MMP7 as Potential Peripheral Blood Biomarkers in Idiopathic Pulmonary Fibrosis. PLOS Medicine 2008, 5: e93. PMID: 18447576, PMCID: PMC2346504, DOI: 10.1371/journal.pmed.0050093.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisInterstitial lung diseaseSubclinical interstitial lung diseasePulmonary fibrosisLung diseaseIPF patientsChronic progressive fibrotic lung diseaseControl individualsAsymptomatic interstitial lung diseaseProgressive fibrotic lung diseaseChronic obstructive pulmonary diseasePotential peripheral blood biomarkerChronic hypersensitivity pneumonitisPeripheral blood biomarkersChronic lung diseaseObstructive pulmonary diseaseFibrotic lung diseaseBronchoalveolar lavage fluidIndependent validation cohortFamilial pulmonary fibrosisProtein signaturesPulmonary diseaseSubstantial morbidityHypersensitivity pneumonitisLavage fluid
2007
Accelerated Variant of Idiopathic Pulmonary Fibrosis: Clinical Behavior and Gene Expression Pattern
Selman M, Carrillo G, Estrada A, Mejia M, Becerril C, Cisneros J, Gaxiola M, Pérez-Padilla R, Navarro C, Richards T, Dauber J, King TE, Pardo A, Kaminski N. Accelerated Variant of Idiopathic Pulmonary Fibrosis: Clinical Behavior and Gene Expression Pattern. PLOS ONE 2007, 2: e482. PMID: 17534432, PMCID: PMC1868965, DOI: 10.1371/journal.pone.0000482.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisMonths of symptomsSubset of patientsRapid progressorsPulmonary fibrosisProgression of IPFBronchoalveolar lavage (BAL) cellular profileActive matrix metalloproteinase-9Kaplan-Meyer methodRapid progressor groupTime of diagnosisBeginning of symptomsEnd-stage diseaseAccelerated clinical courseMatrix metalloproteinase-9Proportional hazards modelMigration/proliferationAdenosine 2B receptorSmooth muscle cellsAlveolar epithelial cellsIPF patientsProgressor groupSlow progressorsClinical courseInsidious onset
2005
Up-Regulation and Profibrotic Role of Osteopontin in Human Idiopathic Pulmonary Fibrosis
Pardo A, Gibson K, Cisneros J, Richards TJ, Yang Y, Becerril C, Yousem S, Herrera I, Ruiz V, Selman M, Kaminski N. Up-Regulation and Profibrotic Role of Osteopontin in Human Idiopathic Pulmonary Fibrosis. PLOS Medicine 2005, 2: e251. PMID: 16128620, PMCID: PMC1198037, DOI: 10.1371/journal.pmed.0020251.Peer-Reviewed Original ResearchMeSH KeywordsBronchoalveolar Lavage FluidCell MovementCell ProliferationCells, CulturedEpithelial CellsExtracellular MatrixFemaleGene Expression ProfilingHumansLungMaleMatrix Metalloproteinase 1Matrix Metalloproteinase 7Middle AgedMolecular Sequence DataOsteopontinPulmonary FibrosisRecombinant ProteinsSialoglycoproteinsTissue Inhibitor of Metalloproteinase-1Up-RegulationConceptsIdiopathic pulmonary fibrosisAlveolar epithelial cellsIPF lungsMMP-7Pulmonary fibrosisEpithelial cellsHuman idiopathic pulmonary fibrosisHuman IPF lungsPrimary human lung fibroblastsMatrix metalloprotease-1 expressionMetalloprotease-1 expressionHuman lung fibroblastsIPF patientsBronchoalveolar lavageProfibrotic effectsProfibrotic roleNormal lungAlveolar epitheliumTissue inhibitorTherapeutic interventionsAnti-CD44Incurable diseaseLungMetalloprotease-1Lethal disorder