2024
A Monocyte-specific Gene-signature Predicts Outcomes in Patients With Idiopathic Pulmonary Fibrosis and Is Reproducible in Peripheral Blood, Bronchoalveolar Lavage, and Lung Tissue
Karampitsakos T, Tourki B, Juan-Guardela B, Perrot C, Marlin K, Arsenault A, Binder H, Wuyts W, Rottoli P, Prasse A, Tzouvelekis A, Restrepo Jaramillo R, Qureshi M, Patel K, Bandyopadhyay D, Kaminski N, Herazo-Maya J. A Monocyte-specific Gene-signature Predicts Outcomes in Patients With Idiopathic Pulmonary Fibrosis and Is Reproducible in Peripheral Blood, Bronchoalveolar Lavage, and Lung Tissue. 2024, a2860-a2860. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a2860.Peer-Reviewed Original ResearchIdentification of abnormal airway niches in the fibrotic lung using spatial transcriptomics
Justet A, Ravaglia C, Zhao A, Adams N, Agshin B, Kaminski N, Tomasseti S, Poletti V. Identification of abnormal airway niches in the fibrotic lung using spatial transcriptomics. Revue Des Maladies Respiratoires 2024, 41: 215. DOI: 10.1016/j.rmr.2024.01.068.Peer-Reviewed Original ResearchVascular endothelial cellsIPF patientsIPF lungsEpithelial cellsLung tissueEndothelial cellsCOVID patientsAirway epithelial cellsAbnormal cell populationsAlveolar epithelial cellsProgression to fibrosisLong COVIDBasaloid cellsControl patientsImmune cellsGene panelFFPE slidesFibrotic lungsProximal airwaysPatientsDistal lungLungBasal cellsCell populationsLong COVID patientsAnti-inflammatory roles of type I interferon signaling in the lung
Feng J, Liu Y, Kim J, Ahangari F, Kaminski N, Bain W, Jie Z, Dela Cruz C, Sharma L. Anti-inflammatory roles of type I interferon signaling in the lung. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2024, 326: l551-l561. PMID: 38375579, PMCID: PMC11380987, DOI: 10.1152/ajplung.00353.2023.Peer-Reviewed Original ResearchType I interferon signalingIfnar1-/- miceI interferon signalingInflammatory cell responseInflammatory responseIfnar1-/-Bleomycin injuryCell responsesWild-type miceBroncho-alveolar lavageElevated inflammatory responsePersistent inflammatory responseChemotherapeutic agent bleomycinAnti-inflammatory roleClinically relevant stimuliAnti-inflammatory mechanismsMyeloid cellsPersistent inflammationLung injuryFibrotic remodelingBacterial clearanceRIG-I signalingNOD-like receptor signalingLung tissueReceptor signaling
2023
SRC and TKS5 mediated podosome formation in fibroblasts promotes extracellular matrix invasion and pulmonary fibrosis
Barbayianni I, Kanellopoulou P, Fanidis D, Nastos D, Ntouskou E, Galaris A, Harokopos V, Hatzis P, Tsitoura E, Homer R, Kaminski N, Antoniou K, Crestani B, Tzouvelekis A, Aidinis V. SRC and TKS5 mediated podosome formation in fibroblasts promotes extracellular matrix invasion and pulmonary fibrosis. Nature Communications 2023, 14: 5882. PMID: 37735172, PMCID: PMC10514346, DOI: 10.1038/s41467-023-41614-x.Peer-Reviewed Original ResearchConceptsPulmonary fibrosisExtracellular matrix invasionLung fibroblastsIdiopathic pulmonary fibrosis patientsIdiopathic pulmonary fibrosisPulmonary fibrosis patientsMatrix invasionPromising therapeutic optionProfibrotic milieuTherapeutic optionsLung tissuePathogenic hallmarkPharmacological targetingFibrosisFibrosis patientsIncurable diseaseEx vivoBleomycinExtracellular matrix componentsTks5 expressionAberrant depositionInvasionMiceFibroblastsSrc kinaseA 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
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 historyElevated 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 patternsMacrophage-derived netrin-1 drives adrenergic nerve–associated lung fibrosis
Gao R, Peng X, Perry C, Sun H, Ntokou A, Ryu C, Gomez JL, Reeves BC, Walia A, Kaminski N, Neumark N, Ishikawa G, Black KE, Hariri LP, Moore MW, Gulati M, Homer RJ, Greif DM, Eltzschig HK, Herzog EL. Macrophage-derived netrin-1 drives adrenergic nerve–associated lung fibrosis. Journal Of Clinical Investigation 2021, 131: e136542. PMID: 33393489, PMCID: PMC7773383, DOI: 10.1172/jci136542.Peer-Reviewed Original ResearchConceptsNetrin-1Lung fibrosisCell-specific knockout miceΑ1-adrenoreceptor blockadeIPF lung tissueNeuronal guidance proteinsNetrin-1 expressionExtracellular matrix accumulationAdrenergic processesAdrenoreceptor antagonismAdrenoreceptor blockadeFibrotic histologyInflammatory scarringIPF cohortAdrenergic nervesΑ1-blockersImproved survivalColorectal carcinomaLung tissueKnockout miceCollagen accumulationFibrosisMatrix accumulationMacrophagesGuidance proteins
2020
Cathepsin 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 ResearchConceptsBronchoalveolar 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 complicationsAssessment of viral RNA in idiopathic pulmonary fibrosis using RNA-seq
Yin Q, Strong MJ, Zhuang Y, Flemington EK, Kaminski N, de Andrade JA, Lasky JA. Assessment of viral RNA in idiopathic pulmonary fibrosis using RNA-seq. BMC Pulmonary Medicine 2020, 20: 81. PMID: 32245461, PMCID: PMC7119082, DOI: 10.1186/s12890-020-1114-1.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisViral RNA expressionViral infectionPulmonary fibrosisPathogenesis of IPFLung biopsy samplesRNA expressionHerpes virus infectionLow-level evidenceReal-time RT-PCRAcute exacerbationControl lungsLung tissueVirus infectionBiopsy samplesSelect virusesPossible associationInfectionRT-PCRStatistical differenceNext-generation sequencingViral RNAFibrosisVirusRNA-seq resultsSmall airways pathology in idiopathic pulmonary fibrosis: a retrospective cohort study
Verleden SE, Tanabe N, McDonough JE, Vasilescu DM, Xu F, Wuyts WA, Piloni D, De Sadeleer L, Willems S, Mai C, Hostens J, Cooper JD, Verbeken EK, Verschakelen J, Galban CJ, Van Raemdonck DE, Colby TV, Decramer M, Verleden GM, Kaminski N, Hackett TL, Vanaudenaerde BM, Hogg JC. Small airways pathology in idiopathic pulmonary fibrosis: a retrospective cohort study. The Lancet Respiratory Medicine 2020, 8: 573-584. PMID: 32061334, PMCID: PMC7292784, DOI: 10.1016/s2213-2600(19)30356-x.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisSevere idiopathic pulmonary fibrosisUnused donor lungsRetrospective cohort studyTerminal bronchiolesMultidetector CTCohort studyDonor lungsPulmonary fibrosisIPF tissueLung tissueMinimal fibrosisVideo-assisted thoracic surgical biopsyDiagnosis of IPFAshcroft fibrosis scoreMultidisciplinary consensus committeeStructural lung injuryInflammatory immune cellsExpiratory flow rateLow lung volumesPotential therapeutic targetMicro-CTLung transplantationVisible airwaysIPF group
2019
The Human Lung Cell Atlas: A High-Resolution Reference Map of the Human Lung in Health and Disease
Schiller HB, Montoro DT, Simon LM, Rawlins EL, Meyer KB, Strunz M, Braga F, Timens W, Koppelman GH, Budinger GRS, Burgess JK, Waghray A, van den Berge M, Theis F, Regev A, Kaminski N, Rajagopal J, Teichmann S, Misharin A, Nawijn M. The Human Lung Cell Atlas: A High-Resolution Reference Map of the Human Lung in Health and Disease. American Journal Of Respiratory Cell And Molecular Biology 2019, 61: 31-41. PMID: 30995076, PMCID: PMC6604220, DOI: 10.1165/rcmb.2018-0416tr.Peer-Reviewed Original ResearchConceptsCell atlasHuman Cell Atlas consortiumCell typesCell-cell interactionsHigh-throughput techniquesFunction of geneticsLung cell typesTranscriptomic analysisDevelopmental processesIndividual cellsMolecular descriptionReference mapTissue microenvironmentDisease mechanismsCellular neighborhoodsHealthy human bodyMolecular profilePersonalized therapeutic regimensCellsLung diseaseTherapeutic regimensImmune cellsLung tissueRecent progressTissue matrix
2018
BPIFA1 regulates lung neutrophil recruitment and interferon signaling during acute inflammation
Britto CJ, Niu N, Khanal S, Huleihel L, Herazo-Maya J, Thompson A, Sauler M, Slade MD, Sharma L, Dela Cruz CS, Kaminski N, Cohn LE. BPIFA1 regulates lung neutrophil recruitment and interferon signaling during acute inflammation. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2018, 316: l321-l333. PMID: 30461288, PMCID: PMC6397348, DOI: 10.1152/ajplung.00056.2018.Peer-Reviewed Original ResearchConceptsLung inflammationAcute inflammationC motif chemokine ligand 10Lung neutrophil recruitmentRegulation of CXCL10Acute lung inflammationBronchoalveolar lavage concentrationsChemokine ligand 10Innate immune responseIFN regulatory factorIntranasal LPSLavage concentrationsLung recruitmentNeutrophil recruitmentWT miceImmune effectsLung diseasePMN recruitmentInflammatory responseLPS treatmentLung tissueInflammatory signalsImmune responseImmunomodulatory propertiesInflammationReducing protein oxidation reverses lung fibrosis
Anathy V, Lahue KG, Chapman DG, Chia SB, Casey DT, Aboushousha R, van der Velden JLJ, Elko E, Hoffman SM, McMillan DH, Jones JT, Nolin JD, Abdalla S, Schneider R, Seward DJ, Roberson EC, Liptak MD, Cousins ME, Butnor KJ, Taatjes DJ, Budd RC, Irvin CG, Ho YS, Hakem R, Brown KK, Matsui R, Bachschmid MM, Gomez JL, Kaminski N, van der Vliet A, Janssen-Heininger YMW. Reducing protein oxidation reverses lung fibrosis. Nature Medicine 2018, 24: 1128-1135. PMID: 29988126, PMCID: PMC6204256, DOI: 10.1038/s41591-018-0090-y.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisLung fibrosisDirect administrationAirways of miceGrowth factor beta 1Transgenic mouse modelFibrotic lungsLung tissueMouse modelAged animalsFibrosisLung epitheliumTherapeutic potentialExcessive depositionBeta 1Transgenic overexpressionOxidative stressExact mechanismAirwayGlrxLungMiceAdministrationOxidative mechanismsThe 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 pneumonitisFibrosis: Lessons from OMICS analyses of the human lung
Yu G, Ibarra GH, Kaminski N. Fibrosis: Lessons from OMICS analyses of the human lung. Matrix Biology 2018, 68: 422-434. PMID: 29567123, PMCID: PMC6015529, DOI: 10.1016/j.matbio.2018.03.014.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisDramatic phenotypic alterationsTranscriptomic studiesOmics analysisOmics profilingOmics technologiesPulmonary fibrosisNumerous aberrationsPhenotypic alterationsMechanistic understandingHuman idiopathic pulmonary fibrosisIPF lung tissueEpithelial cellsCentral roleHuman tissuesIPF samplesNew insightsMolecular featuresIPF lungsInflammatory cellsPatient cohortLung tissueAnimal modelsLethal disorderHuman lung
2017
Modified mesenchymal stem cells using miRNA transduction alter lung injury in a bleomycin model
Huleihel L, Sellares J, Cardenes N, Álvarez D, Faner R, Sakamoto K, Yu G, Kapetanaki MG, Kaminski N, Rojas M. Modified mesenchymal stem cells using miRNA transduction alter lung injury in a bleomycin model. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2017, 313: l92-l103. PMID: 28385811, PMCID: PMC5538868, DOI: 10.1152/ajplung.00323.2016.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersBleomycinBone Marrow CellsCollagenCytokinesDisease Models, AnimalFemaleGene Expression RegulationGene Regulatory NetworksHumansInterleukin-6Leukocyte Common AntigensLung InjuryMesenchymal Stem Cell TransplantationMesenchymal Stem CellsMice, Inbred C57BLMicroRNAsRNA, MessengerSurvival AnalysisTransduction, GeneticTransfectionWeight LossConceptsBone marrow-derived mesenchymal stem cellsMesenchymal stem cellsLung fibrosisLate administrationBleomycin modelMiR-154Different preclinical modelsStem cellsCD45-positive cellsMurine bleomycin modelMarrow-derived mesenchymal stem cellsInitial weight lossLower survival rateAshcroft scoreLung injuryBleomycin instillationFibrotic changesCytokine expressionMice groupsLung tissueOH-prolinePreclinical modelsProtective effectTreatment groupsSurvival rateIdentification and validation of differentially expressed transcripts by RNA-sequencing of formalin-fixed, paraffin-embedded (FFPE) lung tissue from patients with Idiopathic Pulmonary Fibrosis
Vukmirovic M, Herazo-Maya JD, Blackmon J, Skodric-Trifunovic V, Jovanovic D, Pavlovic S, Stojsic J, Zeljkovic V, Yan X, Homer R, Stefanovic B, Kaminski N. Identification and validation of differentially expressed transcripts by RNA-sequencing of formalin-fixed, paraffin-embedded (FFPE) lung tissue from patients with Idiopathic Pulmonary Fibrosis. BMC Pulmonary Medicine 2017, 17: 15. PMID: 28081703, PMCID: PMC5228096, DOI: 10.1186/s12890-016-0356-4.Peer-Reviewed Original ResearchConceptsPaired-end sequencingTranscript profilingHuman genomeRNA sequencingTranscriptomic profilingFFPE lung tissuesSequencing readsLung tissueTotal RNABackgroundIdiopathic pulmonary fibrosisLethal lung diseaseSequencingReadsProfilingPulmonary fibrosisLung diseaseUnknown etiologyIPF tissueGenomeHiSeqTissueTopHat2GenesIPFRNA
2016
Genome-wide imputation study identifies novel HLA locus for pulmonary fibrosis and potential role for auto-immunity in fibrotic idiopathic interstitial pneumonia
Fingerlin TE, Zhang W, Yang IV, Ainsworth HC, Russell PH, Blumhagen RZ, Schwarz MI, Brown KK, Steele MP, Loyd JE, Cosgrove GP, Lynch DA, Groshong S, Collard HR, Wolters PJ, Bradford WZ, Kossen K, Seiwert SD, du Bois RM, Garcia CK, Devine MS, Gudmundsson G, Isaksson HJ, Kaminski N, Zhang Y, Gibson KF, Lancaster LH, Maher TM, Molyneaux PL, Wells AU, Moffatt MF, Selman M, Pardo A, Kim DS, Crapo JD, Make BJ, Regan EA, Walek DS, Daniel JJ, Kamatani Y, Zelenika D, Murphy E, Smith K, McKean D, Pedersen BS, Talbert J, Powers J, Markin CR, Beckman KB, Lathrop M, Freed B, Langefeld CD, Schwartz DA. Genome-wide imputation study identifies novel HLA locus for pulmonary fibrosis and potential role for auto-immunity in fibrotic idiopathic interstitial pneumonia. BMC Genomic Data 2016, 17: 74. PMID: 27266705, PMCID: PMC4895966, DOI: 10.1186/s12863-016-0377-2.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedChromosomes, Human, Pair 6FemaleGene Expression ProfilingGene Expression RegulationGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHLA-DQ beta-ChainsHLA-DRB1 ChainsHumansIdiopathic Pulmonary FibrosisLinkage DisequilibriumMaleMiddle AgedPulmonary FibrosisSequence Analysis, RNAConceptsRisk lociGenome-wide single nucleotide polymorphism (SNP) dataGenome-wide significant associationSingle nucleotide polymorphism dataGenome-wide genotypesRNA sequencing studiesNucleotide polymorphism dataTargeted gene expressionIdiopathic interstitial pneumoniaHigh linkage disequilibriumLung tissueGene regulationHLA allelesRNA sequencingPolymorphism dataRisk allelesGene expressionChromosome 6Protein structureInterstitial pneumoniaHLA regionSequencing studiesGenetic risk allelesAssociation analysisReplication genotyping
2014
Matrix Metalloproteinase-19 Promotes Metastatic Behavior In Vitro and Is Associated with Increased Mortality in Non–Small Cell Lung Cancer
Yu G, Herazo-Maya JD, Nukui T, Romkes M, Parwani A, Juan-Guardela BM, Robertson J, Gauldie J, Siegfried JM, Kaminski N, Kass DJ. Matrix Metalloproteinase-19 Promotes Metastatic Behavior In Vitro and Is Associated with Increased Mortality in Non–Small Cell Lung Cancer. American Journal Of Respiratory And Critical Care Medicine 2014, 190: 780-790. PMID: 25250855, PMCID: PMC4299607, DOI: 10.1164/rccm.201310-1903oc.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerLung cancerEpithelial-mesenchymal transitionLung tumorsMatrix metalloproteinasesProgression of NSCLCNormal lung tissuesHuman lung cancerNSCLC cell linesMultiple NSCLC cell linesLung cancer tumorsMMP19 expressionPoor prognosisCancer deathControl subjectsIncreased MortalityLung tissueNSCLC cellsMolecular pathogenesisPotential biomarkersDisease severityMetastatic behaviorCancerCancer tumors