2024
Single-cell RNA-seq analysis of cell-cell communications in human lung reveals a novel role of VEGF-D in acute lung injury
Yuan Y, Sharma L, Tang W, Raredon M, Ahangari F, Khoury J, Wu D, Niklason L, Kaminski N. Single-cell RNA-seq analysis of cell-cell communications in human lung reveals a novel role of VEGF-D in acute lung injury. Physiology 2024, 39: 1314. DOI: 10.1152/physiol.2024.39.s1.1314.Peer-Reviewed Original ResearchIdiopathic pulmonary fibrosisAcute lung injuryChronic obstructive pulmonary diseaseAcute respiratory distress syndromeAnalysis of cell-cell communicationVEGF-DMicrovascular nicheSingle-cell RNA-seqLung injury modelSingle-cell RNA-seq analysisLung injuryCell-cell communicationLigand-receptor pairsLPS-induced lung injury modelRNA-seqAdjacent cell typesPulmonary diseaseInjury modelHuman lung endothelial cellsBarrier functionImmune cell infiltrationTumor necrosis factor-aRespiratory distress syndromeLung vascular integrityGene expression
2023
Somatic Mutations: The Next Frontier in Demystifying Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis?
Yan X, Kaminski N. Somatic Mutations: The Next Frontier in Demystifying Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis? American Journal Of Respiratory And Critical Care Medicine 2023, 208: 1150-1151. PMID: 37856835, PMCID: PMC10868359, DOI: 10.1164/rccm.202310-1774ed.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseObstructive pulmonary diseaseIdiopathic pulmonary fibrosisPulmonary diseasePulmonary fibrosisFibrosisDiseaseA 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 cancerMorphometrics and Mucosal Immune Features in Lungs With End-stage Chronic Obstructive Pulmonary Disease
De Fays C, Beeckmans H, Kerckhof P, Geudens V, Vermaut A, Gyselinck I, Goos T, Vermant M, Kaes J, Van Slambrouck J, Mohamady Y, Willems L, Aversa L, Maes K, Aelbrecht C, Everaerts S, Mcdonough J, De Sadeleer L, Gohy S, Ambroise J, Wuyts W, Janssens W, Ceulemans L, Van Raemdonck D, Vos R, Hackett T, Hogg J, Kaminski N, Pilette C, Gayan-Ramirez G, Vanaudenaerde B. Morphometrics and Mucosal Immune Features in Lungs With End-stage Chronic Obstructive Pulmonary Disease. 2023, a6145-a6145. DOI: 10.1164/ajrccm-conference.2023.207.1_meetingabstracts.a6145.Peer-Reviewed Original ResearchEnd-stage chronic obstructive pulmonary diseaseChronic obstructive pulmonary diseaseObstructive pulmonary diseasePulmonary diseaseImmune featuresLungDisease
2022
Characterization 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
2021
MicroRNA 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 Susceptibility
2019
BAL 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
2018
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 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 profilesHypercapnia increases airway smooth muscle contractility via caspase-7–mediated miR-133a–RhoA signaling
Shigemura M, Lecuona E, Angulo M, Homma T, Rodríguez DA, Gonzalez-Gonzalez FJ, Welch LC, Amarelle L, Kim SJ, Kaminski N, Budinger GRS, Solway J, Sznajder JI. Hypercapnia increases airway smooth muscle contractility via caspase-7–mediated miR-133a–RhoA signaling. Science Translational Medicine 2018, 10 PMID: 30185650, PMCID: PMC6889079, DOI: 10.1126/scitranslmed.aat1662.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAgedAged, 80 and overAirway ResistanceAnimalsCalciumCalpainCarbon DioxideCaspase 7Chronic DiseaseDown-RegulationEnzyme ActivationFemaleHumansHypercapniaMaleMEF2 Transcription FactorsMice, Inbred C57BLMicroRNAsMiddle AgedMuscle ContractionMuscle, SmoothMyocytes, Smooth MusclePulmonary Disease, Chronic ObstructiveRhoA GTP-Binding ProteinSignal TransductionConceptsChronic obstructive pulmonary diseaseAirway smooth muscle cellsSmooth muscle cellsMouse airway smooth muscle cellsSevere chronic obstructive pulmonary diseaseHuman airway smooth muscle cellsAirway smooth muscle contractilityMuscle cellsCorrection of hypercapniaSmooth muscle cell contractionCohort of patientsObstructive pulmonary diseaseHigh airway resistanceSevere lung diseaseDevelopment of hypercapniaSmooth muscle contractilityMuscle cell contractionRas homolog family member AMyosin light chain phosphorylationAirway contractilityAirway contractionHypercapnic patientsCOPD severityPulmonary diseaseAirway resistanceThe aging lung: tissue telomere shortening in health and disease
Everaerts S, Lammertyn EJ, Martens DS, De Sadeleer LJ, Maes K, van Batenburg AA, Goldschmeding R, van Moorsel CHM, Dupont LJ, Wuyts WA, Vos R, Gayan-Ramirez G, Kaminski N, Hogg JC, Janssens W, Verleden GM, Nawrot TS, Verleden SE, McDonough JE, Vanaudenaerde BM. The aging lung: tissue telomere shortening in health and disease. Respiratory Research 2018, 19: 95. PMID: 29751799, PMCID: PMC5948770, DOI: 10.1186/s12931-018-0794-z.Peer-Reviewed Original ResearchConceptsBronchiolitis obliterans syndromeRestrictive allograft syndromeRelative telomere lengthRegional disease severityShorter RTLNormal lungDisease severityLung agePrior transplantationLung tissueDiseased lungsChronic obstructive pulmonary diseaseChronic hypersensitivity pneumonitisObstructive pulmonary diseaseTelomere lengthNormal human lungPeripheral blood leucocytesDiseased lung tissueDistinct lung regionsAverage relative telomere lengthExplant lungsObliterans syndromeUnused donorPulmonary diseaseHypersensitivity pneumonitis
2016
Integrated Genomics Reveals Convergent Transcriptomic Networks Underlying Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis
Kusko RL, Brothers JF, Tedrow J, Pandit K, Huleihel L, Perdomo C, Liu G, Juan-Guardela B, Kass D, Zhang S, Lenburg M, Martinez F, Quackenbush J, Sciurba F, Limper A, Geraci M, Yang I, Schwartz DA, Beane J, Spira A, Kaminski N. Integrated Genomics Reveals Convergent Transcriptomic Networks Underlying Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2016, 194: 948-960. PMID: 27104832, PMCID: PMC5067817, DOI: 10.1164/rccm.201510-2026oc.Peer-Reviewed Original ResearchMeSH KeywordsAdultEmphysemaFemaleGene Regulatory NetworksHumansHypoxia-Inducible Factor 1, alpha SubunitI-kappa B ProteinsIdiopathic Pulmonary FibrosisMaleMembrane ProteinsMiddle AgedNerve Tissue ProteinsOligonucleotide Array Sequence AnalysisPlatelet-Derived Growth FactorProto-Oncogene Proteins c-mdm2Pulmonary Disease, Chronic ObstructiveConceptsChronic obstructive pulmonary diseaseIdiopathic pulmonary fibrosisObstructive pulmonary diseasePulmonary diseasePulmonary fibrosisNCounter Analysis SystemHypoxia pathwayQuantitative polymerase chain reactionTranscriptomic pathwaysPolymerase chain reactionIndependent cohortEmphysemaIndependent sample setDiseaseGene expression arraysEnvironmental exposuresChain reactionFibrosisLungMolecular mechanismsExpression arraysMiR96Integrative genomics approachTranscriptional regulatory hubsPathway
2015
Suppression of NLRX1 in chronic obstructive pulmonary disease
Kang MJ, Yoon CM, Kim BH, Lee CM, Zhou Y, Sauler M, Homer R, Dhamija A, Boffa D, West AP, Shadel GS, Ting JP, Tedrow JR, Kaminski N, Kim WJ, Lee CG, Oh YM, Elias JA. Suppression of NLRX1 in chronic obstructive pulmonary disease. Journal Of Clinical Investigation 2015, 125: 2458-2462. PMID: 25938787, PMCID: PMC4497738, DOI: 10.1172/jci71747.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseObstructive pulmonary diseaseCigarette smokeAlveolar destructionPulmonary diseaseHuman chronic obstructive pulmonary diseaseExpression of NLRX1Innate immune pathwaysInnate immune responseQuality of lifeCOPD patientsPulmonary functionSubsequent inflammationImmune responseInflammasome activationMurine modelIndependent cohortImmune pathwaysInflammationDisease severityInflammasome responseImportant mediatorCell apoptosisNLRX1Tissue effects
2014
C-X-C Motif Chemokine 13 (CXCL13) Is a Prognostic Biomarker of Idiopathic Pulmonary Fibrosis
Vuga LJ, Tedrow JR, Pandit KV, Tan J, Kass DJ, Xue J, Chandra D, Leader JK, Gibson KF, Kaminski N, Sciurba FC, Duncan SR. C-X-C Motif Chemokine 13 (CXCL13) Is a Prognostic Biomarker of Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2014, 189: 966-974. PMID: 24628285, PMCID: PMC4098096, DOI: 10.1164/rccm.201309-1592oc.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overBiomarkersCase-Control StudiesChemokine CXCL13Disease ProgressionEnzyme-Linked Immunosorbent AssayFemaleHumansIdiopathic Pulmonary FibrosisImmunohistochemistryMaleMiddle AgedOligonucleotide Array Sequence AnalysisPredictive Value of TestsPrognosisPulmonary Disease, Chronic ObstructiveRisk FactorsSensitivity and SpecificitySeverity of Illness IndexConceptsChronic obstructive pulmonary diseaseC motif chemokine 13IPF lungsPrognostic biomarkerB cellsIdiopathic pulmonary fibrosis (IPF) pathogenesisB cell-targeted therapiesAntibody-mediated syndromeDysregulated B cellsPulmonary fibrosis pathogenesisPulmonary artery hypertensionObstructive pulmonary diseaseIdiopathic pulmonary fibrosisSix-month survivalB-cell traffickingAcute exacerbationArtery hypertensionCXCL13 mRNAPlasma CXCL13IPF pathogenesisRespiratory failureLung injuryCXCL13 concentrationsPulmonary diseaseRadiographic emphysemaPneumocystis jirovecii colonization is associated with enhanced Th1 inflammatory gene expression in lungs of humans with chronic obstructive pulmonary disease
Fitzpatrick ME, Tedrow JR, Hillenbrand ME, Lucht L, Richards T, Norris KA, Zhang Y, Sciurba FC, Kaminski N, Morris A. Pneumocystis jirovecii colonization is associated with enhanced Th1 inflammatory gene expression in lungs of humans with chronic obstructive pulmonary disease. Microbiology And Immunology 2014, 58: 202-211. PMID: 24438206, PMCID: PMC4106795, DOI: 10.1111/1348-0421.12135.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseObstructive pulmonary diseaseLung Tissue Research ConsortiumPneumocystis colonizationPulmonary diseaseCOPD pathogenesisLung gene expression profilesChemokine ligands CXCL9Cognate receptor CXCR3Finding of upregulationLungs of humansInflammatory gene expressionLung tissue samplesPotential key pathwaysGene expression profilesPneumocystis jirovecii colonizationReceptor CXCR3Ligands CXCL9Lymphocyte traffickingT lymphocytesInflammatory genesPneumocystis jiroveciiDisease pathogenesisExpression profilesLigand expression
2012
Association Of Plasma Levels Of PTX3 With Clinical Phenotypes Of Chronic Obstructive Pulmonary Disease
Zhang Y, Tedrow J, Zeng Q, Bon J, Chu Y, Duncan S, Weissfeld J, Leader K, Fuhrman C, Branch R, Porter M, Kaminski N, Sciurba F. Association Of Plasma Levels Of PTX3 With Clinical Phenotypes Of Chronic Obstructive Pulmonary Disease. 2012, a2670-a2670. DOI: 10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a2670.Peer-Reviewed Original ResearchChronic obstructive pulmonary diseaseObstructive pulmonary diseasePulmonary diseasePlasma levelsClinical phenotypePTX3Disease
2011
A Variant In The Promoter Of MUC5B Is Associated With Idiopathic Pulmonary Fibrosis And Not Chronic Obstructive Pulmonary Disease
Zhang Y, Noth I, Gibson K, Ma S, Richards T, Bon J, Lindell K, Branch R, Nicolae D, Sciurba F, Garcia A, Kaminski N. A Variant In The Promoter Of MUC5B Is Associated With Idiopathic Pulmonary Fibrosis And Not Chronic Obstructive Pulmonary Disease. 2011, a6395-a6395. DOI: 10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a6395.Peer-Reviewed Original ResearchChronic obstructive pulmonary diseaseObstructive pulmonary diseaseIdiopathic pulmonary fibrosisPulmonary diseasePulmonary fibrosisFibrosisDiseaseMUC5B
2009
The Influence of Radiographic Phenotype and Smoking Status on Peripheral Blood Biomarker Patterns in Chronic Obstructive Pulmonary Disease
Bon JM, Leader JK, Weissfeld JL, Coxson HO, Zheng B, Branch RA, Kondragunta V, Lee JS, Zhang Y, Choi AM, Lokshin AE, Kaminski N, Gur D, Sciurba FC. The Influence of Radiographic Phenotype and Smoking Status on Peripheral Blood Biomarker Patterns in Chronic Obstructive Pulmonary Disease. PLOS ONE 2009, 4: e6865. PMID: 19718453, PMCID: PMC2730536, DOI: 10.1371/journal.pone.0006865.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseObstructive pulmonary diseaseCurrent smoking statusAirway thickeningSmoking statusPulmonary diseaseBiomarker patternsSerum biomarker patternsSerum biomarker profilesSerum inflammatory proteinsParenchymal phenotypesMeasurements of FEV1Cross-sectional studyMultiplex protein arrayUnique biomarker patternsQuantitative CT measurementsCOPD syndromePhysiologic obstructionSecond percentAirway remodelingExpiratory volumeInflammatory markersParenchymal destructionScreening cohortBiological therapy
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
Effects of Exercise Training on Quadriceps Muscle Gene Expression in Chronic Obstructive Pulmonary Disease.
RadomAizik S, Kaminski N, Hayek S, Halkin H, Cooper D, BenDov I. Effects of Exercise Training on Quadriceps Muscle Gene Expression in Chronic Obstructive Pulmonary Disease. Cardiopulmonary Physical Therapy Journal 2007, 18: 26-27. DOI: 10.1097/01823246-200718030-00009.Peer-Reviewed Original ResearchChronic obstructive pulmonary diseaseObstructive pulmonary diseasePulmonary diseaseExercise trainingMuscle gene expressionGene expressionDiseaseEffects of exercise training on quadriceps muscle gene expression in chronic obstructive pulmonary disease
Radom-Aizik S, Kaminski N, Hayek S, Halkin H, Cooper DM, Ben-Dov I. Effects of exercise training on quadriceps muscle gene expression in chronic obstructive pulmonary disease. Journal Of Applied Physiology 2007, 102: 1976-1984. PMID: 17483440, DOI: 10.1152/japplphysiol.00577.2006.Peer-Reviewed Original ResearchMeSH KeywordsAgedCase-Control StudiesCluster AnalysisEnergy MetabolismExerciseGene ExpressionGene Expression ProfilingHumansMaleOligonucleotide Array Sequence AnalysisOxidative StressOxygen ConsumptionProteasome Endopeptidase ComplexPulmonary Disease, Chronic ObstructiveQuadriceps MuscleReproducibility of ResultsReverse Transcriptase Polymerase Chain ReactionRNA, MessengerUbiquitinConceptsChronic obstructive pulmonary diseaseObstructive pulmonary diseaseCOPD patientsPulmonary diseaseExercise trainingAge-matched healthy menMuscle gene expressionHigh expressionSkeletal muscle functionExercise capacityGene expressionWalk testHealthy menControl subjectsNeedle biopsyMuscle functionVastus lateralisPatientsOxidative stressTraining responseFunctional parametersDiseaseTissue stressExpressionGene pathways