Featured Publications
Airway basal cells show a dedifferentiated KRT17highPhenotype and promote fibrosis in idiopathic pulmonary fibrosis
Jaeger B, Schupp JC, Plappert L, Terwolbeck O, Artysh N, Kayser G, Engelhard P, Adams TS, Zweigerdt R, Kempf H, Lienenklaus S, Garrels W, Nazarenko I, Jonigk D, Wygrecka M, Klatt D, Schambach A, Kaminski N, Prasse A. Airway basal cells show a dedifferentiated KRT17highPhenotype and promote fibrosis in idiopathic pulmonary fibrosis. Nature Communications 2022, 13: 5637. PMID: 36163190, PMCID: PMC9513076, DOI: 10.1038/s41467-022-33193-0.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisAirway basal cellsPulmonary fibrosisNovel mouse xenograft modelEffect of saracatinibBasal cellsLimited treatment optionsMouse xenograft modelLung developmental processesConnectivity Map analysisExtracellular matrix depositionIPF lungsBronchial brushSevere fibrosisTreatment optionsBronchial brushingsNRG miceHealthy volunteersXenograft modelCyst-like structuresProfibrotic changesAlveolar compartmentFatal diseaseFibrosisPotent Src inhibitor
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 Research
2021
Elevated 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 ResearchConceptsIL-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 controlsLong noncoding RNA TINCR is a novel regulator of human bronchial epithelial cell differentiation state
Omote N, Sakamoto K, Li Q, Schupp JC, Adams T, Ahangari F, Chioccioli M, DeIuliis G, Hashimoto N, Hasegawa Y, Kaminski N. Long noncoding RNA TINCR is a novel regulator of human bronchial epithelial cell differentiation state. Physiological Reports 2021, 9: e14727. PMID: 33527707, PMCID: PMC7851438, DOI: 10.14814/phy2.14727.Peer-Reviewed Original ResearchConceptsTerminal differentiation-induced lncRNANormal human bronchial epithelial cellsTINCR overexpressionCell differentiationNotch genesTissue developmentBronchial epithelial cellsExtracellular matrix organizationCell phenotypeRNA sequencing analysisNumerous biological functionsRole of lncRNAsCell differentiation stateEpithelial cellsHuman bronchial epithelial cellsCiliated cell differentiationStaufen1 proteinNovel regulatorBasal cell phenotypeDownstream regulatorsRNA immunoprecipitationBiological functionsCritical regulatorDifferential expressionDifferentiation stateElevated plasma level of Pentraxin 3 is associated with emphysema and mortality in smokers
Zhang Y, Tedrow J, Nouraie M, Li X, Chandra D, Bon J, Kass DJ, Fuhrman CR, Leader JK, Duncan SR, Kaminski N, Sciurba FC. Elevated plasma level of Pentraxin 3 is associated with emphysema and mortality in smokers. Thorax 2021, 76: 335-342. PMID: 33479043, PMCID: PMC8249179, DOI: 10.1136/thoraxjnl-2020-215356.Peer-Reviewed Original ResearchConceptsAirflow obstructionPlasma levelsLung tissueEmphysema severitySmoking-related lung diseaseAssociation of lungExpiratory airflow obstructionFormer tobacco smokersLevels of PTX3PTX3 gene expressionElevated plasma levelsHyaluronic acid levelsBlood of subjectsPlasma PTX3PTX3 levelsLung functionTobacco exposureClinical outcomesTobacco smokersLung diseasePentraxin 3Predictive biomarkersPTX3 expressionLower riskDisease patterns
2020
Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis
Tsukui T, Sun KH, Wetter JB, Wilson-Kanamori JR, Hazelwood LA, Henderson NC, Adams TS, Schupp JC, Poli SD, Rosas IO, Kaminski N, Matthay MA, Wolters PJ, Sheppard D. Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis. Nature Communications 2020, 11: 1920. PMID: 32317643, PMCID: PMC7174390, DOI: 10.1038/s41467-020-15647-5.Peer-Reviewed Original ResearchConceptsCollagen-producing cellsSitu hybridization showDisease-relevant phenotypesCell atlasDistinct localizationExpression of CTHRC1Fibrotic lungsDifferent compartmentsPulmonary fibrosisDistinct anatomical localizationCellsCTHRC1Murine lungFibroblastsIdiopathic pulmonary fibrosisAdoptive transfer experimentsLocalizationSubpopulationsComplex architectureTransfer experimentsFibroblastic fociPathologic fibrosisPathologic scarringScleroderma patientsSimilar heterogeneity
2019
Plasma 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 insights
2018
An HDAC9-MALAT1-BRG1 complex mediates smooth muscle dysfunction in thoracic aortic aneurysm
Lino Cardenas CL, Kessinger CW, Cheng Y, MacDonald C, MacGillivray T, Ghoshhajra B, Huleihel L, Nuri S, Yeri AS, Jaffer FA, Kaminski N, Ellinor P, Weintraub NL, Malhotra R, Isselbacher EM, Lindsay ME. An HDAC9-MALAT1-BRG1 complex mediates smooth muscle dysfunction in thoracic aortic aneurysm. Nature Communications 2018, 9: 1009. PMID: 29520069, PMCID: PMC5843596, DOI: 10.1038/s41467-018-03394-7.Peer-Reviewed Original ResearchMeSH KeywordsActomyosinAnimalsAortaAortic Aneurysm, ThoracicCell LineCell NucleusChromatinDisease Models, AnimalDNA HelicasesDNA MethylationFemaleFluorescent Antibody TechniqueHistone DeacetylasesHistonesHumansMaleMiceMice, KnockoutMuscle, Smooth, VascularMutationMyocytes, Smooth MuscleNuclear ProteinsPhenotypePrimary Cell CultureRepressor ProteinsRNA InterferenceRNA, Long NoncodingRNA, Small InterferingSignal TransductionTranscription FactorsTransforming Growth Factor betaConceptsChromatin-remodeling enzyme BRG1Contractile protein gene expressionProtein gene expressionLong noncoding RNA MALAT1Noncoding RNA MALAT1Bind chromatinTGF-β signalingTrimethylation modificationActomyosin cytoskeletonEpigenetic pathwaysContractile protein expressionGene expressionSimilar phenotypeRNA MALAT1Ternary complexBRG1HDAC9VSMC dysfunctionAortic aneurysmCytoskeletonProtein expressionPotential common mechanismsCommon mechanismSmooth muscle dysfunctionMutations
2017
Integrin alpha 11 in the regulation of the myofibroblast phenotype: implications for fibrotic diseases
Bansal R, Nakagawa S, Yazdani S, van Baarlen J, Venkatesh A, Koh AP, Song WM, Goossens N, Watanabe H, Beasley MB, Powell CA, Storm G, Kaminski N, van Goor H, Friedman SL, Hoshida Y, Prakash J. Integrin alpha 11 in the regulation of the myofibroblast phenotype: implications for fibrotic diseases. Experimental & Molecular Medicine 2017, 49: e396-e396. PMID: 29147013, PMCID: PMC5704196, DOI: 10.1038/emm.2017.213.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationDisease Models, AnimalFibrosisGene Expression RegulationGene Knockdown TechniquesHedgehog ProteinsHepatic Stellate CellsHumansImmunohistochemistryIntegrin alpha ChainsKidney DiseasesLiver CirrhosisMiceMyofibroblastsPhenotypeSignal TransductionTransforming Growth Factor betaConceptsHepatic stellate cellsFibrotic parametersMouse modelStellate cellsTissue fibrosisIntegrin alpha 11Alpha 11Smooth muscle actin-positive myofibroblastsLiver fibrosis mouse modelHuman hepatic stellate cellsMyofibroblast phenotypeFibrosis mouse modelPromising therapeutic targetActin-positive myofibroblastsCause of mortalityGrowth factor βAberrant extracellular matrixImpaired contractilityFibrogenic signalingFibrotic organsFibrogenic processExtracellular matrixTherapeutic targetOrgan fibrosisMyofibroblastic differentiation
2015
Integrative phenotyping framework (iPF): integrative clustering of multiple omics data identifies novel lung disease subphenotypes
Kim S, Herazo-Maya JD, Kang DD, Juan-Guardela BM, Tedrow J, Martinez FJ, Sciurba FC, Tseng GC, Kaminski N. Integrative phenotyping framework (iPF): integrative clustering of multiple omics data identifies novel lung disease subphenotypes. BMC Genomics 2015, 16: 924. PMID: 26560100, PMCID: PMC4642618, DOI: 10.1186/s12864-015-2170-4.Peer-Reviewed Original ResearchRationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis Study. Alpha-1 Protocol
Strange C, Senior RM, Sciurba F, O’Neal S, Morris A, Wisniewski SR, Bowler R, Hochheiser HS, Becich MJ, Zhang Y, Leader JK, Methé BA, Kaminski N, Sandhaus RA, Group* F. Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis Study. Alpha-1 Protocol. Annals Of The American Thoracic Society 2015, 12: 1551-1560. PMID: 26153726, PMCID: PMC4627425, DOI: 10.1513/annalsats.201503-143oc.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAlpha 1-Antitrypsin DeficiencyBronchoalveolar LavageCross-Sectional StudiesExercise ToleranceFemaleGenomicsGenotypeHumansMaleMicrobiotaMiddle AgedPhenotypeProspective StudiesPulmonary Disease, Chronic ObstructivePulmonary EmphysemaResearch DesignRespiratory Function TestsSarcoidosisTomography, X-Ray ComputedConceptsAlpha-1 antitrypsin deficiencyAugmentation therapyBronchoalveolar lavageAntitrypsin deficiencyClinical presentationPiZZ individualsAlpha-1-antitrypsin augmentation therapyAlpha-1 antitrypsin genotypeChronic obstructive pulmonary disease phenotypesPulmonary function testingAge 35 yearsVariable clinical presentationCross-sectional studyAlpha-1 antitrypsinIntermediate outcome measuresPulmonary disease phenotypesUnique genetic causeExercise capacityTherapeutic trialsChest tomographyClinical symptomsCOPD pathogenesisCOPD phenotypesFunction testingCOPD Study
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 characteristics
2013
Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study
Noth I, Zhang Y, Ma SF, Flores C, Barber M, Huang Y, Broderick SM, Wade MS, Hysi P, Scuirba J, Richards TJ, Juan-Guardela BM, Vij R, Han MK, Martinez FJ, Kossen K, Seiwert SD, Christie JD, Nicolae D, Kaminski N, Garcia J. Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study. The Lancet Respiratory Medicine 2013, 1: 309-317. PMID: 24429156, PMCID: PMC3894577, DOI: 10.1016/s2213-2600(13)70045-6.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide significanceSingle nucleotide polymorphismsAssociation studiesThree-stage genome-wide association studyDiscovery Genome-Wide Association StudiesGene expression profiling dataGenetic variantsWide association studyRare genetic variantsAdditional common variantsDNA samplesMinor alleleCommon single nucleotide polymorphismsNovel variantsPulmonary Fibrosis FoundationDatabase of GenotypesGenetic lociTollip expressionNucleotide polymorphismsProfiling dataSNP genotypesCommon variantsIPF susceptibilityCommon alleles
2012
Integrative Assessment of Chlorine-Induced Acute Lung Injury in Mice
Leikauf GD, Pope-Varsalona H, Concel VJ, Liu P, Bein K, Berndt A, Martin TM, Ganguly K, Jang AS, Brant KA, Dopico RA, Upadhyay S, Di YP, Li Q, Hu Z, Vuga LJ, Medvedovic M, Kaminski N, You M, Alexander DC, McDunn JE, Prows DR, Knoell DL, Fabisiak JP. Integrative Assessment of Chlorine-Induced Acute Lung Injury in Mice. American Journal Of Respiratory Cell And Molecular Biology 2012, 47: 234-244. PMID: 22447970, PMCID: PMC3423464, DOI: 10.1165/rcmb.2012-0026oc.Peer-Reviewed Original ResearchConceptsCandidate genesGenetic basisProtein catabolic processAcute lung injuryLung injuryHaplotype association mappingC57BLKS/JSingle nucleotide polymorphism associationsAssociation mappingMetabolomic profilingProtein transportCatabolic processTranscript levelsHaplotype mappingChromosome 1Chlorine-induced acute lung injuryAmino acid carrierSNP associationsReal-time PCRGenesGenetic associationMean survival timeRecognition sitesProfilingPromoter SNPs
2007
Towards Systems Biology of Human Pulmonary Fibrosis
Studer SM, Kaminski N. Towards Systems Biology of Human Pulmonary Fibrosis. Annals Of The American Thoracic Society 2007, 4: 85-91. PMID: 17202296, PMCID: PMC2647618, DOI: 10.1513/pats.200607-139jg.Peer-Reviewed Original ResearchConceptsSystems biology approachBiology approachSystems biologyHigh-throughput genotypingHigh-throughput technologiesMicroarray resultsBiological processesQuantitative phenotypingEnvironmental stimuliFibrosis researchMultiple pathwaysLung phenotypeBiologyGlobal analysisHuman pulmonary fibrosisGenetic polymorphismsIdiopathic pulmonary fibrosisComputational toolsPulmonary fibrosisSystemwide viewHigh-resolution profilesPhenotypePathwayLethal lung diseasePolymorphism
2005
Abnormal Vascular Phenotypes in Patients With Idiopathic Pulmonary Fibrosis and Secondary Pulmonary Hypertension
Gagermeier J, Dauber J, Yousem S, Gibson K, Kaminski N. Abnormal Vascular Phenotypes in Patients With Idiopathic Pulmonary Fibrosis and Secondary Pulmonary Hypertension. CHEST Journal 2005, 128: 601s. PMID: 16373857, DOI: 10.1378/chest.128.6_suppl.601s.Peer-Reviewed Original ResearchCan Blood Gene Expression Predict Which Patients with Multiple Sclerosis Will Respond to Interferon?
Kaminski N, Achiron A. Can Blood Gene Expression Predict Which Patients with Multiple Sclerosis Will Respond to Interferon? PLOS Medicine 2005, 2: e33. PMID: 15736992, PMCID: PMC549584, DOI: 10.1371/journal.pmed.0020033.Peer-Reviewed Original Research
2003
Global Expression Profiling of Fibroblast Responses to Transforming Growth Factor-β1 Reveals the Induction of Inhibitor of Differentiation-1 and Provides Evidence of Smooth Muscle Cell Phenotypic Switching
Chambers RC, Leoni P, Kaminski N, Laurent GJ, Heller RA. Global Expression Profiling of Fibroblast Responses to Transforming Growth Factor-β1 Reveals the Induction of Inhibitor of Differentiation-1 and Provides Evidence of Smooth Muscle Cell Phenotypic Switching. American Journal Of Pathology 2003, 162: 533-546. PMID: 12547711, PMCID: PMC1851161, DOI: 10.1016/s0002-9440(10)63847-3.Peer-Reviewed Original ResearchMeSH KeywordsCell DivisionCell LineCell SurvivalFetusFibroblastsGene Expression ProfilingHelix-Loop-Helix MotifsHumansImmunohistochemistryInhibitor of Differentiation Protein 1Inhibitor of Differentiation ProteinsLungMuscle, SmoothNeoplasm ProteinsPhenotypeRepressor ProteinsRNA, MessengerTranscription FactorsTranscription, GeneticTransforming Growth Factor betaTransforming Growth Factor beta1ConceptsMajor functional categoriesHelix transcription factorGlobal gene expressionNumber of genesCell lineage commitmentGlobal expression profilingDominant-negative antagonistSmooth muscle cell phenotypic switchingProtein levelsSmooth muscle myosin heavy chainInduction of inhibitorMuscle myosin heavy chainTransformation of fibroblastsImmediate early genesTranscriptional regulatorsTranscriptional programsExtracellular matrix protein depositionTranscriptional programmingProtein biosynthesisGene groupsLineage commitmentCytoskeletal reorganizationTranscription factorsFunctional categoriesCell signaling