Featured Publications
microRNA-33 deficiency in macrophages enhances autophagy, improves mitochondrial homeostasis, and protects against lung fibrosis
Ahangari F, Price N, Malik S, Chioccioli M, Bärnthaler T, Adams T, Kim J, Pradeep S, Ding S, Cosme C, Rose K, McDonough J, Aurelien N, Ibarra G, Omote N, Schupp J, DeIuliis G, Nunez J, Sharma L, Ryu C, Dela Cruz C, Liu X, Prasse A, Rosas I, Bahal R, Fernandez-Hernando C, Kaminski N. microRNA-33 deficiency in macrophages enhances autophagy, improves mitochondrial homeostasis, and protects against lung fibrosis. JCI Insight 2023, 8: e158100. PMID: 36626225, PMCID: PMC9977502, DOI: 10.1172/jci.insight.158100.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutophagyBleomycinHomeostasisHumansIdiopathic Pulmonary FibrosisMacrophagesMiceMicroRNAsMitochondriaConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisMiR-33MiR-33 levelsSpecific genetic ablationBronchoalveolar lavage cellsNovel therapeutic approachesMitochondrial homeostasisFatty acid metabolismMacrophages protectsBleomycin injuryLavage cellsLung fibrosisHealthy controlsInflammatory responseTherapeutic approachesImmunometabolic responsesCholesterol effluxFibrosisFatal diseasePharmacological inhibitionSterol regulatory element-binding protein (SREBP) genesGenetic ablationMacrophagesEx vivo mouse
2024
Noninvasive assessment of the lung inflammation-fibrosis axis by targeted imaging of CMKLR1
Mannes P, Adams T, Farsijani S, Barnes C, Latoche J, Day K, Nedrow J, Ahangari F, Kaminski N, Lee J, Tavakoli S. Noninvasive assessment of the lung inflammation-fibrosis axis by targeted imaging of CMKLR1. Science Advances 2024, 10: eadm9817. PMID: 38896611, PMCID: PMC11186491, DOI: 10.1126/sciadv.adm9817.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisFibrotic lung diseaseRisk stratificationMurine modelLung fibrosisLung diseaseModel of bleomycin-induced lung fibrosisBleomycin-induced lung fibrosisImaging biomarkersMurine model of bleomycin-induced lung fibrosisBronchoalveolar lavage cellsMonocyte-derived macrophagesPositron emission tomographyInflammatory endotypesPulmonary fibrosisLavage cellsPoor survivalNoninvasive assessmentTherapeutic monitoringEmission tomographyCMKLR1FibrosisClinical trajectoryLungLung regions
2023
An integrated cell atlas of the lung in health and disease
Sikkema L, Ramírez-Suástegui C, Strobl D, Gillett T, Zappia L, Madissoon E, Markov N, Zaragosi L, Ji Y, Ansari M, Arguel M, Apperloo L, Banchero M, Bécavin C, Berg M, Chichelnitskiy E, Chung M, Collin A, Gay A, Gote-Schniering J, Hooshiar Kashani B, Inecik K, Jain M, Kapellos T, Kole T, Leroy S, Mayr C, Oliver A, von Papen M, Peter L, Taylor C, Walzthoeni T, Xu C, Bui L, De Donno C, Dony L, Faiz A, Guo M, Gutierrez A, Heumos L, Huang N, Ibarra I, Jackson N, Kadur Lakshminarasimha Murthy P, Lotfollahi M, Tabib T, Talavera-López C, Travaglini K, Wilbrey-Clark A, Worlock K, Yoshida M, van den Berge M, Bossé Y, Desai T, Eickelberg O, Kaminski N, Krasnow M, Lafyatis R, Nikolic M, Powell J, Rajagopal J, Rojas M, Rozenblatt-Rosen O, Seibold M, Sheppard D, Shepherd D, Sin D, Timens W, Tsankov A, Whitsett J, Xu Y, Banovich N, Barbry P, Duong T, Falk C, Meyer K, Kropski J, Pe’er D, Schiller H, Tata P, Schultze J, Teichmann S, Misharin A, Nawijn M, Luecken M, Theis F. An integrated cell atlas of the lung in health and disease. Nature Medicine 2023, 29: 1563-1577. PMID: 37291214, PMCID: PMC10287567, DOI: 10.1038/s41591-023-02327-2.Peer-Reviewed Original ResearchConceptsCell atlasGene modulesCell typesCell type definitionsHuman Cell AtlasSingle-cell technologiesSingle-cell datasetsUndescribed cell typeMultiple lung diseasesCell statesMarker genesMonocyte-derived macrophagesDistal axisStudy of diseasesHuman tissuesAnnotationAtlasGenesSPP1DiversityExpressionTreesLimited numberCellsNew data
2022
Microenvironmental sensing by fibroblasts controls macrophage population size
Zhou X, Franklin RA, Adler M, Carter TS, Condiff E, Adams TS, Pope SD, Philip NH, Meizlish ML, Kaminski N, Medzhitov R. Microenvironmental sensing by fibroblasts controls macrophage population size. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2205360119. PMID: 35930670, PMCID: PMC9371703, DOI: 10.1073/pnas.2205360119.Peer-Reviewed Original ResearchConceptsCell typesDensity-dependent gene expressionTGF-β target genesDiverse cell typesActin-dependent mechanismLineage-specific growth factorsDistinct cell typesGrowth factor availabilityActivation of YAP1Different cell typesExpression programsMicroenvironmental sensingTranscriptional coactivatorTarget genesGene expressionPopulation sizeFactor availabilityPopulation numbersTissue environmentTissue integrityHippoProliferation of macrophagesYAP1Animal tissuesMechanical forces
2021
Macrophage-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 ResearchMeSH KeywordsAnimalsBleomycinFemaleLungMacrophagesMaleMiceMice, TransgenicNetrin-1NorepinephrinePulmonary FibrosisConceptsNetrin-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
2016
Plexin C1 deficiency permits synaptotagmin 7–mediated macrophage migration and enhances mammalian lung fibrosis
Peng X, Moore M, Mathur A, Zhou Y, Sun H, Gan Y, Herazo‐Maya J, Kaminski N, Hu X, Pan H, Ryu C, Osafo‐Addo A, Homer RJ, Feghali‐Bostwick C, Fares W, Gulati M, Hu B, Lee C, Elias JA, Herzog EL. Plexin C1 deficiency permits synaptotagmin 7–mediated macrophage migration and enhances mammalian lung fibrosis. The FASEB Journal 2016, 30: 4056-4070. PMID: 27609773, PMCID: PMC5102121, DOI: 10.1096/fj.201600373r.Peer-Reviewed Original ResearchConceptsLung fibrosisPlexin C1Macrophage migrationPulmonary fibrosisBone marrow-derived cellsSynaptotagmin-7Idiopathic pulmonary fibrosisInterstitial lung diseaseMarrow-derived cellsTGF-β1 overexpressionFatal conditionLung diseaseMonocyte migrationUnrecognized observationCollagen accumulationFibrosisMice showBoyden chamberGenetic deletionLungMouse macrophagesSemaphorin receptorsMacrophagesC1s deficiencyDeficiency
2015
Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs
Phinney DG, Di Giuseppe M, Njah J, Sala E, Shiva S, St Croix CM, Stolz DB, Watkins SC, Di YP, Leikauf GD, Kolls J, Riches DW, Deiuliis G, Kaminski N, Boregowda SV, McKenna DH, Ortiz LA. Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs. Nature Communications 2015, 6: 8472. PMID: 26442449, PMCID: PMC4598952, DOI: 10.1038/ncomms9472.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArrestinsBlotting, WesternCell-Derived MicroparticlesExosomesExtracellular VesiclesFlow CytometryHumansMacrophagesMesenchymal Stem CellsMiceMicroRNAsMicroscopy, ElectronMitochondriaMitophagyMyeloid Differentiation Factor 88Oxidative StressReceptors, ImmunologicSignal TransductionSilicosisToll-Like Receptor 4Toll-Like Receptor 9Toll-Like ReceptorsConceptsMesenchymal stem cellsStem cellsDomain-containing protein 1Stem cell nicheHealthy mitochondrial functionHaematopoietic stem cellsCell nichePlasma membraneToll-like receptor signalingIntracellular oxidative stressMitochondrial functionExtracellular vesiclesMicro RNAsReceptor signalingProtein 1MitophagyMSC survivalMitochondriaOxidative stressMacrophage functionVesiclesCellsRecent studiesMacrophage activationMacrophages
2009
Systemic Inhibition of NF-κB Activation Protects from Silicosis
Di Giuseppe M, Gambelli F, Hoyle GW, Lungarella G, Studer SM, Richards T, Yousem S, McCurry K, Dauber J, Kaminski N, Leikauf G, Ortiz LA. Systemic Inhibition of NF-κB Activation Protects from Silicosis. PLOS ONE 2009, 4: e5689. PMID: 19479048, PMCID: PMC2682759, DOI: 10.1371/journal.pone.0005689.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCytokinesEpithelial CellsFemaleGene Expression RegulationGenes, DominantHumansI-kappa B ProteinsLungLung TransplantationMacrophagesMaleMiceMice, Inbred C57BLMiddle AgedNF-kappa BNF-KappaB Inhibitor alphaNitrilesPrognosisRNA, MessengerSilicon DioxideSilicosisSulfonesTumor Necrosis Factor-alphaConceptsNF-kappaB activationLung transplantationSystemic inhibitionLung injuryCollagen depositionLung transplant databaseIdiopathic pulmonary fibrosisComplex lung diseaseNecrosis factor alphaPathogenesis of silicosisIkappaB-alpha phosphorylationInnate immune responsePotential therapeutic strategyNF-kappaB inhibitionMouse experimental modelIPF patientsLung graftsGraft rejectionOverall survivalSurvival benefitTransplant databasePulmonary fibrosisPoor outcomeInflammatory cellsLung disease
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