Featured Publications
A lung targeted miR-29 mimic as a therapy for pulmonary fibrosis
Chioccioli M, Roy S, Newell R, Pestano L, Dickinson B, Rigby K, Herazo-Maya J, Jenkins G, Ian S, Saini G, Johnson SR, Braybrooke R, Yu G, Sauler M, Ahangari F, Ding S, DeIuliis J, Aurelien N, Montgomery RL, Kaminski N. A lung targeted miR-29 mimic as a therapy for pulmonary fibrosis. EBioMedicine 2022, 85: 104304. PMID: 36265417, PMCID: PMC9587275, DOI: 10.1016/j.ebiom.2022.104304.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisNon-human primatesPulmonary fibrosisAnimal modelsPro-fibrotic genesAnti-fibrotic efficacyMiR-29 mimicsHuman peripheral bloodMiR-29b levelsHuman lung fibroblastsIPF patientsIPF diagnosisPeripheral bloodReduced fibrosisAdverse findingsPotential therapyLung slicesTGF-β1Relevant dosesLung fibroblastsNIH-NHLBIFibrosisTherapyCollagen productionProfibrotic gene program
2022
Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in Preclinical Models of Pulmonary Fibrosis.
Ahangari F, Becker C, Foster DG, Chioccioli M, Nelson M, Beke K, Wang X, Justet A, Adams T, Readhead B, Meador C, Correll K, Lili LN, Roybal HM, Rose KA, Ding S, Barnthaler T, Briones N, DeIuliis G, Schupp JC, Li Q, Omote N, Aschner Y, Sharma L, Kopf KW, Magnusson B, Hicks R, Backmark A, Dela Cruz CS, Rosas I, Cousens LP, Dudley JT, Kaminski N, Downey GP. Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in Preclinical Models of Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2022, 206: 1463-1479. PMID: 35998281, PMCID: PMC9757097, DOI: 10.1164/rccm.202010-3832oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisHuman precision-cut lung slicesPrecision-cut lung slicesPulmonary fibrosisNormal human lung fibroblastsEpithelial-mesenchymal transitionHuman lung fibroblastsFibrogenic pathwaysPreclinical modelsMurine modelLung slicesSrc kinase inhibitorLung fibroblastsKinase inhibitorsAmelioration of fibrosisSelective Src kinase inhibitorHuman lung fibrosisWhole lung extractsPotential therapeutic efficacyIPF diseaseIPF treatmentLung functionInflammatory cascadeLung fibrosisAntifibrotic efficacy
2018
PD-1 up-regulation on CD4+ T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-β1 production
Celada LJ, Kropski JA, Herazo-Maya JD, Luo W, Creecy A, Abad AT, Chioma OS, Lee G, Hassell NE, Shaginurova GI, Wang Y, Johnson JE, Kerrigan A, Mason WR, Baughman RP, Ayers GD, Bernard GR, Culver DA, Montgomery CG, Maher TM, Molyneaux PL, Noth I, Mutsaers SE, Prele CM, Peebles R, Newcomb DC, Kaminski N, Blackwell TS, Van Kaer L, Drake WP. PD-1 up-regulation on CD4+ T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-β1 production. Science Translational Medicine 2018, 10 PMID: 30257954, PMCID: PMC6263177, DOI: 10.1126/scitranslmed.aar8356.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsBleomycinCD4-Positive T-LymphocytesCell ProliferationCollagen Type IDisease Models, AnimalFemaleFibroblastsGene Expression RegulationHumansIdiopathic Pulmonary FibrosisInterleukin-17MaleMiceMiddle AgedProgrammed Cell Death 1 ReceptorRNA, MessengerSarcoidosisSTAT3 Transcription FactorTh17 CellsTransforming Growth Factor beta1Up-RegulationConceptsIdiopathic pulmonary fibrosisPD-1Pulmonary fibrosisT cellsCollagen-1 productionPD-1 pathway blockadeCell death ligand 1T helper 17 (Th17) cellsPD-1 regulationIL-17A expressionProgressive inflammatory diseaseDeath ligand 1Helper 17 cellsT cell subsetsCell death 1Limited therapeutic optionsTGF-β1 productionLung disease pathophysiologyHuman lung fibroblastsPredominant CD4Bleomycin administrationIL-17ADeath-1Therapeutic optionsCell subsets
2017
Extracellular Mitochondrial DNA Is Generated by Fibroblasts and Predicts Death in Idiopathic Pulmonary Fibrosis
Ryu C, Sun H, Gulati M, Herazo-Maya J, Chen Y, Osafo-Addo A, Brandsdorfer C, Winkler J, Blaul C, Faunce J, Pan H, Woolard T, Tzouvelekis A, Antin-Ozerkis DE, Puchalski JT, Slade M, Gonzalez AL, Bogenhagen DF, Kirillov V, Feghali-Bostwick C, Gibson K, Lindell K, Herzog RI, Dela Cruz CS, Mehal W, Kaminski N, Herzog EL, Trujillo G. Extracellular Mitochondrial DNA Is Generated by Fibroblasts and Predicts Death in Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2017, 196: 1571-1581. PMID: 28783377, PMCID: PMC5754440, DOI: 10.1164/rccm.201612-2480oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisNormal human lung fibroblastsExtracellular mitochondrial DNABronchoalveolar lavageIPF fibroblastsPulmonary fibrosisInnate immune ligandsEvent-free survivalSmooth muscle actin expressionMtDNA concentrationsSmooth muscle actin-expressing myofibroblastsGrowth factor-β1Muscle actin expressionHuman lung fibroblastsTGF-β1 stimulationExtracellular mtDNAIPF cohortClinical outcomesControl subjectsDisease progressionGlycolytic reprogrammingSoluble mediatorsTGF-β1Factor-β1Immune ligands
2016
SH2 Domain–Containing Phosphatase-2 Is a Novel Antifibrotic Regulator in Pulmonary Fibrosis
Tzouvelekis A, Yu G, Lino Cardenas CL, Herazo-Maya JD, Wang R, Woolard T, Zhang Y, Sakamoto K, Lee H, Yi JS, DeIuliis G, Xylourgidis N, Ahangari F, Lee PJ, Aidinis V, Herzog EL, Homer R, Bennett AM, Kaminski N. SH2 Domain–Containing Phosphatase-2 Is a Novel Antifibrotic Regulator in Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2016, 195: 500-514. PMID: 27736153, PMCID: PMC5378419, DOI: 10.1164/rccm.201602-0329oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisProfibrotic stimuliLung fibroblastsChronic fatal lung diseaseMyofibroblast differentiationPrimary human lung fibroblastsFatal lung diseaseNovel therapeutic strategiesVivo therapeutic effectPotential therapeutic usefulnessHuman lung fibroblastsMouse lung fibroblastsDismal prognosisFibroblastic fociLung fibrosisLung diseaseBleomycin modelTherapeutic effectTherapeutic usefulnessTherapeutic strategiesTherapeutic targetTransgenic miceFibrosisSHP2 overexpression
2015
VCAM-1 is a TGF-β1 inducible gene upregulated in idiopathic pulmonary fibrosis
Agassandian M, Tedrow JR, Sembrat J, Kass DJ, Zhang Y, Goncharova EA, Kaminski N, Mallampalli RK, Vuga LJ. VCAM-1 is a TGF-β1 inducible gene upregulated in idiopathic pulmonary fibrosis. Cellular Signalling 2015, 27: 2467-2473. PMID: 26386411, PMCID: PMC4684430, DOI: 10.1016/j.cellsig.2015.09.003.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisVCAM-1IPF subjectsPulmonary fibrosisVascular cell adhesion molecule-1Lethal interstitial lung diseaseVCAM-1 protein levelsCell adhesion molecule-1Interstitial lung diseaseLungs of subjectsProtein levelsHigher plasma levelsVCAM-1 mRNAAdhesion molecule-1Pulmonary diffusion capacityHuman lung fibroblastsIPF lungsLung functionFibrotic fociVital capacityLung diseaseUnknown etiologyControl subjectsPlasma levelsCell cycle arrestFK506-Binding Protein 10, a Potential Novel Drug Target for Idiopathic Pulmonary Fibrosis
Staab-Weijnitz CA, Fernandez IE, Knüppel L, Maul J, Heinzelmann K, Juan-Guardela BM, Hennen E, Preissler G, Winter H, Neurohr C, Hatz R, Lindner M, Behr J, Kaminski N, Eickelberg O. FK506-Binding Protein 10, a Potential Novel Drug Target for Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2015, 192: 455-467. PMID: 26039104, PMCID: PMC4595665, DOI: 10.1164/rccm.201412-2233oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPrimary human lung fibroblastsGrowth factor-β1Endoplasmic reticulum stressPulmonary fibrosisFKBP10 expressionLung fibrosisNovel drug targetsControl subjectsFactor-β1Protein 10Immunofluorescent stainingReticulum stressReverse transcriptase-polymerase chain reactionQuantitative reverse transcriptase-polymerase chain reactionTranscriptase-polymerase chain reactionSmooth muscle actinPotential novel drug targetsHuman lung fibroblastsCollagen secretionDrug targetsWestern blot analysisProfibrotic mediatorsU.S. cohortGerman cohortA Novel Genomic Signature with Translational Significance for Human Idiopathic Pulmonary Fibrosis
Bauer Y, Tedrow J, de Bernard S, Birker-Robaczewska M, Gibson KF, Guardela BJ, Hess P, Klenk A, Lindell KO, Poirey S, Renault B, Rey M, Weber E, Nayler O, Kaminski N. A Novel Genomic Signature with Translational Significance for Human Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory Cell And Molecular Biology 2015, 52: 217-231. PMID: 25029475, PMCID: PMC4370242, DOI: 10.1165/rcmb.2013-0310oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisHuman idiopathic pulmonary fibrosisLung fibrosis modelGrowth factor-β1IPF lungsPulmonary fibrosisFibrosis modelFactor-β1Therapeutic interventionsDevastating lung diseasePrimary human lung fibroblastsLung Tissue Research ConsortiumGene marker setsPotential therapeutic interventionsHuman lung fibroblastsEpithelial A549 cellsHuman epithelial A549 cellsBleomycin instillationLung fibrosisControl lungsLung diseaseControl cohortControl subjectsTranslational significanceNovel treatments
2013
Cartilage Oligomeric Matrix Protein in Idiopathic Pulmonary Fibrosis
Vuga LJ, Milosevic J, Pandit K, Ben-Yehudah A, Chu Y, Richards T, Sciurba J, Myerburg M, Zhang Y, Parwani AV, Gibson KF, Kaminski N. Cartilage Oligomeric Matrix Protein in Idiopathic Pulmonary Fibrosis. PLOS ONE 2013, 8: e83120. PMID: 24376648, PMCID: PMC3869779, DOI: 10.1371/journal.pone.0083120.Peer-Reviewed Original ResearchMeSH KeywordsAgedCartilage Oligomeric Matrix ProteinCells, CulturedCollagen Type ICollagen Type I, alpha 1 ChainExtracellular MatrixFemaleFibroblastsGene Expression RegulationHumansIdiopathic Pulmonary FibrosisLungMaleMiddle AgedPlasminogen Activator Inhibitor 1RNA, Small InterferingSignal TransductionSmad3 ProteinTransforming Growth Factor beta1VimentinConceptsIdiopathic pulmonary fibrosisCartilage oligomeric matrix proteinIPF lungsNormal human lung fibroblastsForce vital capacityHuman lung fibroblastsTGF-β1Oligomeric matrix proteinPulmonary fibrosisLung fibroblastsSerum COMP concentrationTGF-β1 activityEpithelial cell hyperplasiaMatrix proteinsLung restrictionWestern blot analysisExtracellular matrix depositionIPF patientsTime-dependent fashionDisease activityMedian survivalVital capacityCell hyperplasiaControl lungsBlood draw
2012
Profibrotic Role of miR-154 in Pulmonary Fibrosis
Milosevic J, Pandit K, Magister M, Rabinovich E, Ellwanger DC, Yu G, Vuga LJ, Weksler B, Benos PV, Gibson KF, McMillan M, Kahn M, Kaminski N. Profibrotic Role of miR-154 in Pulmonary Fibrosis. American Journal Of Respiratory Cell And Molecular Biology 2012, 47: 879-887. PMID: 23043088, PMCID: PMC3547095, DOI: 10.1165/rcmb.2011-0377oc.Peer-Reviewed Original ResearchMeSH KeywordsCase-Control StudiesCell MovementCell ProliferationCells, CulturedChromosomes, Human, Pair 14Cyclin-Dependent Kinase Inhibitor p15FibroblastsGene ExpressionHumansLungMicroRNAsMultigene FamilyOligonucleotide Array Sequence AnalysisPulmonary FibrosisRNA InterferenceTranscriptomeTransforming Growth Factor beta1Wnt Signaling PathwayConceptsIdiopathic pulmonary fibrosisNormal human lung fibroblastsMiR-154IPF lungsPulmonary fibrosisIPF fibroblastsProgressive interstitial lung diseaseInterstitial lung diseaseWnt/β-catenin pathwayHuman lung fibroblastsΒ-catenin pathwayTGF-β1 stimulationBinding of Smad3Quantitative RT-PCRLung diseaseProfibrotic roleExpression of microRNAsICG-001MiR-134Unknown originMiR-382MiR-487bProliferative effectLung fibroblastsMiR-410
2005
Up-Regulation and Profibrotic Role of Osteopontin in Human Idiopathic Pulmonary Fibrosis
Pardo A, Gibson K, Cisneros J, Richards TJ, Yang Y, Becerril C, Yousem S, Herrera I, Ruiz V, Selman M, Kaminski N. Up-Regulation and Profibrotic Role of Osteopontin in Human Idiopathic Pulmonary Fibrosis. PLOS Medicine 2005, 2: e251. PMID: 16128620, PMCID: PMC1198037, DOI: 10.1371/journal.pmed.0020251.Peer-Reviewed Original ResearchMeSH KeywordsBronchoalveolar Lavage FluidCell MovementCell ProliferationCells, CulturedEpithelial CellsExtracellular MatrixFemaleGene Expression ProfilingHumansLungMaleMatrix Metalloproteinase 1Matrix Metalloproteinase 7Middle AgedMolecular Sequence DataOsteopontinPulmonary FibrosisRecombinant ProteinsSialoglycoproteinsTissue Inhibitor of Metalloproteinase-1Up-RegulationConceptsIdiopathic pulmonary fibrosisAlveolar epithelial cellsIPF lungsMMP-7Pulmonary fibrosisEpithelial cellsHuman idiopathic pulmonary fibrosisHuman IPF lungsPrimary human lung fibroblastsMatrix metalloprotease-1 expressionMetalloprotease-1 expressionHuman lung fibroblastsIPF patientsBronchoalveolar lavageProfibrotic effectsProfibrotic roleNormal lungAlveolar epitheliumTissue inhibitorTherapeutic interventionsAnti-CD44Incurable diseaseLungMetalloprotease-1Lethal disorder