Featured Publications
Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function
Yu G, Tzouvelekis A, Wang R, Herazo-Maya JD, Ibarra GH, Srivastava A, de Castro JPW, DeIuliis G, Ahangari F, Woolard T, Aurelien N, Arrojo e Drigo R, Gan Y, Graham M, Liu X, Homer RJ, Scanlan TS, Mannam P, Lee PJ, Herzog EL, Bianco AC, Kaminski N. Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function. Nature Medicine 2017, 24: 39-49. PMID: 29200204, PMCID: PMC5760280, DOI: 10.1038/nm.4447.Peer-Reviewed Original Research
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 kinase
2018
Reducing 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 mechanisms
2015
Enhancing Autophagy with Drugs or Lung-directed Gene Therapy Reverses the Pathological Effects of Respiratory Epithelial Cell Proteinopathy*
Hidvegi T, Stolz DB, Alcorn JF, Yousem SA, Wang J, Leme AS, Houghton AM, Hale P, Ewing M, Cai H, Garchar EA, Pastore N, Annunziata P, Kaminski N, Pilewski J, Shapiro SD, Pak SC, Silverman GA, Brunetti-Pierri N, Perlmutter DH. Enhancing Autophagy with Drugs or Lung-directed Gene Therapy Reverses the Pathological Effects of Respiratory Epithelial Cell Proteinopathy*. Journal Of Biological Chemistry 2015, 290: 29742-29757. PMID: 26494620, PMCID: PMC4705969, DOI: 10.1074/jbc.m115.691253.Peer-Reviewed Original ResearchConceptsSpontaneous pulmonary fibrosisPulmonary fibrosisΑ1-antitrypsin ZPathological effectsSevere pulmonary fibrosisRespiratory epithelial cellsPiZ miceRestrictive deficitsActivation of autophagyLeukocyte infiltrationSurfactant protein AAnimal modelsC deficiencyFibrosisProteinopathiesSkeletal muscleEpithelial cellsIntracellular accumulationAutophagolysosomal systemLungMiceAttractive targetAutophagyDrugsRecent studies
2012
Retinoic Acid–related Orphan Receptor-α Is Induced in the Setting of DNA Damage and Promotes Pulmonary Emphysema
Shi Y, Cao J, Gao J, Zheng L, Goodwin A, An CH, Patel A, Lee JS, Duncan SR, Kaminski N, Pandit KV, Rosas IO, Choi AM, Morse D. Retinoic Acid–related Orphan Receptor-α Is Induced in the Setting of DNA Damage and Promotes Pulmonary Emphysema. American Journal Of Respiratory And Critical Care Medicine 2012, 186: 412-419. PMID: 22744720, PMCID: PMC5450975, DOI: 10.1164/rccm.201111-2023oc.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersCells, CulturedDisease Models, AnimalDNA DamageDNA RepairGene Expression ProfilingHumansLungMiceMice, Inbred C57BLMice, Neurologic MutantsNuclear Receptor Subfamily 1, Group F, Member 1Oligonucleotide Array Sequence AnalysisPulmonary Disease, Chronic ObstructivePulmonary EmphysemaTobacco Smoke PollutionConceptsRetinoic acid-related orphan receptorAcid-related orphan receptorCigarette smoke extractLungs of patientsPathogenesis of emphysemaRORA expressionCigarette smokeAirspace enlargementSmoke extractCigarette smoke exposureSmoke-induced emphysemaOrphan receptorDNA damageActive smokingLung transplantationSmoke exposureLung cancerPulmonary emphysemaLung tissueEmphysemaPatientsGene expression profilingApoptotic cell deathMiceEnhanced susceptibility
2011
Integrative metabolome and transcriptome profiling reveals discordant energetic stress between mouse strains with differential sensitivity to acrolein‐induced acute lung injury
Fabisiak JP, Medvedovic M, Alexander DC, McDunn JE, Concel VJ, Bein K, Jang AS, Berndt A, Vuga LJ, Brant KA, Pope‐Varsalona H, Dopico RA, Ganguly K, Upadhyay S, Li Q, Hu Z, Kaminski N, Leikauf GD. Integrative metabolome and transcriptome profiling reveals discordant energetic stress between mouse strains with differential sensitivity to acrolein‐induced acute lung injury. Molecular Nutrition & Food Research 2011, 55: 1423-1434. PMID: 21823223, PMCID: PMC3482455, DOI: 10.1002/mnfr.201100291.Peer-Reviewed Original ResearchConceptsAcute lung injuryLung injuryAcrolein exposureMouse lungMouse strainsJ mouse lungEnvironmental tobacco smokeChain amino acid metabolismFatty acid β-oxidationLung metabolomeJ miceSM/J miceTobacco smokeAcrolein treatmentRespiratory irritantsAmino acid metabolismLungEnergetic stressInjuryAcid metabolismSM/JΒ-oxidationMiceIntegrative metabolomeHealth hazards
2010
Functional Genomics of Chlorine-induced Acute Lung Injury in Mice
Leikauf GD, Pope-Varsalona H, Concel VJ, Liu P, Bein K, Brant KA, Dopico RA, Di YP, Jang AS, Dietsch M, Medvedovic M, Li Q, Vuga LJ, Kaminski N, You M, Prows DR. Functional Genomics of Chlorine-induced Acute Lung Injury in Mice. Annals Of The American Thoracic Society 2010, 7: 294-296. PMID: 20601635, PMCID: PMC3136967, DOI: 10.1513/pats.201001-005sm.Peer-Reviewed Original ResearchConceptsAcute lung injuryChlorine-induced acute lung injuryLung injuryMouse strainsMean survival timeGene-targeted miceSusceptibility candidate genesSupportive measuresSurvival timeDivergent strainsInjuryCandidate genesCritical candidate genesFunctional genomics approachMiceAdditional genetic analysesMolecular eventsFunctional significanceFunctional genomicsGenomic approachesChlorine exposureGenetic basisNovel insightsGenetic analysisHospitalizationCandidate Susceptibility Genes Identified By Genomewide Analysis Of Chloride-induced Acute Lung Injury In Mice
Leikauf G, Pope-Varsalona H, Concel V, Liu P, Bein K, Brant K, Dopico R, Di Y, Jang A, Medvedovic M, Li Q, Vega L, Kaminski N, You M, Prows D. Candidate Susceptibility Genes Identified By Genomewide Analysis Of Chloride-induced Acute Lung Injury In Mice. 2010, a5370-a5370. DOI: 10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a5370.Peer-Reviewed Original Research
2008
Mitogen-Activated Protein Kinases Regulate Susceptibility to Ventilator-Induced Lung Injury
Dolinay T, Wu W, Kaminski N, Ifedigbo E, Kaynar AM, Szilasi M, Watkins SC, Ryter SW, Hoetzel A, Choi AM. Mitogen-Activated Protein Kinases Regulate Susceptibility to Ventilator-Induced Lung Injury. PLOS ONE 2008, 3: e1601. PMID: 18270588, PMCID: PMC2223071, DOI: 10.1371/journal.pone.0001601.Peer-Reviewed Original ResearchConceptsVentilator-induced lung injuryMatrix metalloproteinase-8Lung injuryInflammatory lung injuryWild-type miceMechanical ventilationProtein kinase kinase 3C57/BL6 wild-type miceLung injury parametersTerminal kinase 1C-JunLung vascular permeabilityProtein kinaseKinase 1Kinase 3Edema formationMitogen-activated protein kinase kinase 3Metalloproteinase-8Vascular permeabilityMitogen-activated protein kinase pathwayInjuryInjury parametersComprehensive gene expression profilingMiceProtein leakageA Role for the Receptor for Advanced Glycation End Products in Idiopathic Pulmonary Fibrosis
Englert JM, Hanford LE, Kaminski N, Tobolewski JM, Tan RJ, Fattman CL, Ramsgaard L, Richards TJ, Loutaev I, Nawroth PP, Kasper M, Bierhaus A, Oury TD. A Role for the Receptor for Advanced Glycation End Products in Idiopathic Pulmonary Fibrosis. American Journal Of Pathology 2008, 172: 583-591. PMID: 18245812, PMCID: PMC2258251, DOI: 10.2353/ajpath.2008.070569.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisAdvanced glycation end productsRAGE-null micePulmonary fibrosisGlycation end productsIPF pathogenesisMouse modelNovel therapeutic targetHealthy adult animalsIPF patientsWild-type controlsDismal prognosisSevere fibrosisIPF tissueEffective therapyFibrotic lungsTherapeutic targetHistological scoringFibrosisLoss of RAGECell surface receptorsAdult animalsMiceEnd productsSoluble isoform
2003
Loss of integrin αvβ6-mediated TGF-β activation causes Mmp12-dependent emphysema
Morris DG, Huang X, Kaminski N, Wang Y, Shapiro SD, Dolganov G, Glick A, Sheppard D. Loss of integrin αvβ6-mediated TGF-β activation causes Mmp12-dependent emphysema. Nature 2003, 422: 169-173. PMID: 12634787, DOI: 10.1038/nature01413.Peer-Reviewed Original ResearchConceptsTGF-β activationLungs of miceActive TGF-β1Pulmonary gene expressionHeterodimeric cell-surface proteinsTransgenic expressionPulmonary emphysemaMMP12 expressionTGF-β1Functional alterationsΒ6 integrinIntegrin αvβ6Latent TGFMarked inductionEmphysemaGrowth factorMacrophage metalloelastaseCell surface proteinsActivation pathwayMiceTGFActivationCell growthIntegrinsExpression
2002
Gene expression analysis reveals matrilysin as a key regulator of pulmonary fibrosis in mice and humans
Zuo F, Kaminski N, Eugui E, Allard J, Yakhini Z, Ben-Dor A, Lollini L, Morris D, Kim Y, DeLustro B, Sheppard D, Pardo A, Selman M, Heller RA. Gene expression analysis reveals matrilysin as a key regulator of pulmonary fibrosis in mice and humans. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 6292-6297. PMID: 11983918, PMCID: PMC122942, DOI: 10.1073/pnas.092134099.Peer-Reviewed Original ResearchConceptsPulmonary fibrosisFibrotic lungsHuman pulmonary fibrosisPotential therapeutic targetGene expression analysisClinical diseaseSmooth muscleKnockout miceTherapeutic targetFibrosisHuman tissue samplesUntreatable groupLungTissue samplesMolecular pathwaysGlobal gene expression analysisExtracellular matrix formationMiceExpression analysisMatrilysinMolecular mechanismsKey regulatorGene expression patternsExpression patternsOligonucleotide microarrays
2001
TGF-β is a critical mediator of acute lung injury
Pittet J, Griffiths M, Geiser T, Kaminski N, Dalton S, Huang X, Brown L, Gotwals P, Koteliansky V, Matthay M, Sheppard D. TGF-β is a critical mediator of acute lung injury. Journal Of Clinical Investigation 2001, 107: 1537-1544. PMID: 11413161, PMCID: PMC200192, DOI: 10.1172/jci11963.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, NeoplasmBleomycinBlood-Air BarrierCells, CulturedEndotoxinsGlutathioneIntegrinsMiceMice, KnockoutProtein Serine-Threonine KinasesPulmonary AlveoliPulmonary EdemaReceptor, Transforming Growth Factor-beta Type IIReceptors, Transforming Growth Factor betaRespiratory Distress SyndromeTransforming Growth Factor betaConceptsAcute lung injuryPulmonary edemaLung injuryAlveolar epithelial permeabilityWild-type miceEscherichia coli endotoxinColi endotoxinEffective treatmentEpithelial permeabilityIntegrin alphavbeta6Pharmacologic inhibitionEdemaCritical mediatorUntreatable disorderLocal activationIntracellular glutathioneInjuryMiceActivationLungTGFBleomycinEndotoxin
2000
Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis
Kaminski N, Allard J, Pittet J, Zuo F, Griffiths M, Morris D, Huang X, Sheppard D, Heller R. Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 1778-1783. PMID: 10677534, PMCID: PMC26512, DOI: 10.1073/pnas.97.4.1778.Peer-Reviewed Original ResearchConceptsPulmonary fibrosisLung inflammationBleomycin administrationSusceptible miceMultiple time pointsFibrotic responseFibrosisFibrotic diseasesInflammationMore effective strategiesGene expressionTime pointsMiceBeta6 subunitMolecular mechanismsSequential inductionGene expression patternsExpression patternsNull mutationResponseEffective strategyLungExpressionBleomycinGene expression programs