2023
Genetic analyses of chr11p15.5 region identify MUC5AC-MUC5B associated with asthma-related phenotypes
Li X, Li H, Christenson S, Castro M, Denlinger L, Erzurum S, Fahy J, Gaston B, Israel E, Jarjour N, Levy B, Mauger D, Moore W, Zein J, Kaminski N, Wenzel S, Woodruff P, Bleecker E, Meyers D, Program F. Genetic analyses of chr11p15.5 region identify MUC5AC-MUC5B associated with asthma-related phenotypes. Journal Of Asthma 2023, 60: 1824-1835. PMID: 36946148, PMCID: PMC10524756, DOI: 10.1080/02770903.2023.2193631.Peer-Reviewed Original ResearchLow CC16 mRNA Expression Levels in Bronchial Epithelial Cells Are Associated with Asthma Severity.
Li X, Guerra S, Ledford JG, Kraft M, Li H, Hastie AT, Castro M, Denlinger LC, Erzurum SC, Fahy JV, Gaston B, Israel E, Jarjour NN, Levy BD, Mauger DT, Moore WC, Zein J, Kaminski N, Wenzel SE, Woodruff PG, Meyers DA, Bleecker ER. Low CC16 mRNA Expression Levels in Bronchial Epithelial Cells Are Associated with Asthma Severity. American Journal Of Respiratory And Critical Care Medicine 2023, 207: 438-451. PMID: 36066606, PMCID: PMC9940145, DOI: 10.1164/rccm.202206-1230oc.Peer-Reviewed Original ResearchConceptsBronchial epithelial cellsMRNA expression levelsAsthma severityT2 biomarkersAsthma susceptibilityT2 inflammationExpression levelsSevere Asthma Research ProgramSystemic corticosteroid useLower pulmonary functionEpithelial cellsAsthma-related phenotypesCorticosteroid useAsthma exacerbationsPulmonary functionAsthma developmentAsthma endotypesAsthma progressionInflammation biomarkersInflammation genesHost defenseCC16Th2 genesSeverityBiomarkers
2021
Machine learning implicates the IL-18 signaling axis in severe asthma
Camiolo MJ, Zhou X, Wei Q, Bittar H, Kaminski N, Ray A, Wenzel S. Machine learning implicates the IL-18 signaling axis in severe asthma. JCI Insight 2021, 6: e149945. PMID: 34591794, PMCID: PMC8663569, DOI: 10.1172/jci.insight.149945.Peer-Reviewed Original ResearchConceptsLung functionIL-18NF-κBTranscriptional hallmarksExacerbation-prone asthmaSevere asthma pathogenesisSubgroup of patientsVariable natural historySevere Asthma Research Program (SARP) cohortDownstream NF-κBMixed inflammatory processActivator protein-1 (AP-1) activationPathobiological underpinningsCorticosteroid exposureSevere asthmaAsthma clustersAsthma pathogenesisPatient morbidityInflammatory processProtein-1 activationExternal cohortLung tissuePatient clustersAP-1 activityNatural history
2020
Genetic analyses identify GSDMB associated with asthma severity, exacerbations, and antiviral pathways
Li X, Christenson SA, Modena B, Li H, Busse WW, Castro M, Denlinger LC, Erzurum SC, Fahy JV, Gaston B, Hastie AT, Israel E, Jarjour NN, Levy BD, Moore WC, Woodruff PG, Kaminski N, Wenzel SE, Bleecker ER, Meyers DA, Program N. Genetic analyses identify GSDMB associated with asthma severity, exacerbations, and antiviral pathways. Journal Of Allergy And Clinical Immunology 2020, 147: 894-909. PMID: 32795586, PMCID: PMC7876167, DOI: 10.1016/j.jaci.2020.07.030.Peer-Reviewed Original ResearchConceptsExpression quantitative trait loci (eQTL) analysisQuantitative trait locus (QTL) analysisSingle nucleotide polymorphismsGasdermin BMultiple single nucleotide polymorphismsFunctional genesExpression levelsLocus analysisAntiviral pathwaysGenes/single-nucleotide polymorphismsWhole genome sequencesGene expression dataEpithelial cellsImmune system pathwaysHigh expression levelsHuman bronchial epithelial cellsIFN regulatory factorGPI attachmentGSDMB expressionAsthma susceptibilityGenetic analysisGene expressionPathway analysisBronchial epithelial cellsRegulatory factorsExpression 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 traitsGenesExpressionSialylation of MUC4β N-glycans by ST6GAL1 orchestrates human airway epithelial cell differentiation associated with Type-2 inflammation
Zhou X, Kinlough CL, Hughey RP, Jin M, Inoue H, Etling E, Modena BD, Kaminski N, Bleecker ER, Meyers DA, Jarjour NN, Trudeau JB, Holguin F, Ray A, Wenzel SE. Sialylation of MUC4β N-glycans by ST6GAL1 orchestrates human airway epithelial cell differentiation associated with Type-2 inflammation. JCI Insight 2019, 4 PMID: 30730306, PMCID: PMC6483602, DOI: 10.1172/jci.insight.122475.Peer-Reviewed Original ResearchConceptsHuman airway epithelial cellsEpithelial dysfunctionPrimary human airway epithelial cellsAirway epithelial cell differentiationT2-high asthmaType 2 inflammationAirway epithelial cellsGoblet cell differentiationEpithelial cell proliferationAirway specimensT2 biomarkersAsthmatic patientsSputum supernatantsT2 inflammationIL-13Cell differentiationAsthmaEpithelial cell differentiationSpecific mucinsEpithelial cell fateΒ-galactoside αEpithelial glycoproteinEpithelial cellsPotential targetEpithelial differentiation
2017
Toward Precision Medicine of Symptom Control in Asthma
Gomez JL, Kaminski N. Toward Precision Medicine of Symptom Control in Asthma. American Journal Of Respiratory And Critical Care Medicine 2017, 195: 147-148. PMID: 28084831, PMCID: PMC5394790, DOI: 10.1164/rccm.201608-1600ed.Commentaries, Editorials and Letters
2016
Gene Expression Correlated with Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease
Modena BD, Bleecker ER, Busse WW, Erzurum SC, Gaston BM, Jarjour NN, Meyers DA, Milosevic J, Tedrow JR, Wu W, Kaminski N, Wenzel SE. Gene Expression Correlated with Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease. American Journal Of Respiratory And Critical Care Medicine 2016, 195: 1449-1463. PMID: 27984699, PMCID: PMC5470748, DOI: 10.1164/rccm.201607-1407oc.Peer-Reviewed Original ResearchConceptsWeighted gene coexpression network analysisGene coexpression network analysisCoexpression network analysisGene expressionBiological processesAirway epithelial cell gene expressionEpithelial cell gene expressionNetwork of genesGene expression networksGene network modulesAsthma susceptibility lociT2 gene expressionCell gene expressionGene expression studiesNeuronal functionEpithelial growthMultiple molecular mechanismsExpression networksT2 genesGene networksUnderlying biological processesHub genesExpression studiesBiological insightsNetwork analysisExpression 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
2014
Gene Expression in Relation to Exhaled Nitric Oxide Identifies Novel Asthma Phenotypes with Unique Biomolecular Pathways
Modena BD, Tedrow JR, Milosevic J, Bleecker ER, Meyers DA, Wu W, Bar-Joseph Z, Erzurum SC, Gaston BM, Busse WW, Jarjour NN, Kaminski N, Wenzel SE. Gene Expression in Relation to Exhaled Nitric Oxide Identifies Novel Asthma Phenotypes with Unique Biomolecular Pathways. American Journal Of Respiratory And Critical Care Medicine 2014, 190: 1363-1372. PMID: 25338189, PMCID: PMC4294630, DOI: 10.1164/rccm.201406-1099oc.Peer-Reviewed Original ResearchConceptsEpithelial cell gene expressionCell gene expressionGene expressionAirway epithelial cell gene expressionGene expression patternsSevere Asthma Research ProgramActin cytoskeletonGene clusterGenomic studiesGene transcriptionGene pathwaysMolecular basisExpression patternsAsthma phenotypesWnt pathwayMicroarray platformGenesNovel pathwayPhenotypeBiomolecular pathwaysNeuronal functionPathwayUnadjusted p-valuesExpressionBiological characteristicsAn airway epithelial iNOS–DUOX2–thyroid peroxidase metabolome drives Th1/Th2 nitrative stress in human severe asthma
Voraphani N, Gladwin MT, Contreras AU, Kaminski N, Tedrow JR, Milosevic J, Bleecker ER, Meyers DA, Ray A, Ray P, Erzurum SC, Busse WW, Zhao J, Trudeau JB, Wenzel SE. An airway epithelial iNOS–DUOX2–thyroid peroxidase metabolome drives Th1/Th2 nitrative stress in human severe asthma. Mucosal Immunology 2014, 7: 1175-1185. PMID: 24518246, PMCID: PMC4130801, DOI: 10.1038/mi.2014.6.Peer-Reviewed Original ResearchConceptsInducible nitric oxide synthaseHuman airway epithelial cellsDual oxidase 2Severe asthmaNitrative stressThyroid peroxidaseIL-13Ex vivoSevere refractory asthmaNitric oxide synthaseTh2 cytokine expressionAirway epithelial cellsRefractory asthmaLower interleukinHigher interferonCytokine expressionOxide synthaseOxidase 2AsthmaIFNEpithelial cellsEpithelial cell systemSuperoxide dismutaseRNA knockdownEndogenous peroxidase
2011
Genomic Differences Distinguish the Myofibroblast Phenotype of Distal Lung Fibroblasts from Airway Fibroblasts
Zhou X, Wu W, Hu H, Milosevic J, Konishi K, Kaminski N, Wenzel SE. Genomic Differences Distinguish the Myofibroblast Phenotype of Distal Lung Fibroblasts from Airway Fibroblasts. American Journal Of Respiratory Cell And Molecular Biology 2011, 45: 1256-1262. PMID: 21757679, PMCID: PMC3262668, DOI: 10.1165/rcmb.2011-0065oc.Peer-Reviewed Original ResearchConceptsGenomic differencesMicroarray analysisC-Jun N-terminal kinaseExtracellular matrix-associated moleculesMyofibroblast-like characteristicsDistinct genomic differencesN-terminal kinasePotential functional implicationsQuantitative real-time PCRMatrix-associated moleculesCytoskeletal organizationGene OntologyActin bindingLung fibroblastsReal-time PCRMyofibroblast phenotypeFunctional implicationsParenchymal fibroblastsAirway fibroblastsDifferentiated fibroblastsPathway activationDifferent phenotypesRegional fibroblastsFibroblastsPhenotype
2007
A Functional and Regulatory Map of Asthma
Novershtern N, Itzhaki Z, Manor O, Friedman N, Kaminski N. A Functional and Regulatory Map of Asthma. American Journal Of Respiratory Cell And Molecular Biology 2007, 38: 324-336. PMID: 17921359, PMCID: PMC2258452, DOI: 10.1165/rcmb.2007-0151oc.Peer-Reviewed Original ResearchMeSH KeywordsAlgorithmsAllergensAnimalsAsthmaDisease Models, AnimalGene Expression ProfilingHumansHypersensitivityImmunity, InnateInterleukin-13MiceMice, Inbred AMice, Inbred BALB CMice, Inbred C3HMice, KnockoutModels, BiologicalOligonucleotide Array Sequence AnalysisOvalbuminProtein Interaction MappingReproducibility of ResultsSystems BiologyTranscription, GeneticTransforming Growth Factor beta1ConceptsCo-regulated gene modulesGene expression compendiumProtein interaction networksModule network analysisMouse microarray datasetsSystems-level viewExpression compendiumRegulatory mapGene modulesModule membersFunctional themesInteraction networksKey regulatorAnimal modelsMicroarray datasetsGeneral inductionAnnotation setsChronic inflammatory airway diseasesMorbidity of asthmaInflammatory airway diseasesMechanisms of asthmaAdaptive immune responsesSystem-level approachSimilar roleDistinct responses