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 programThyroid 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 ResearchmicroRNA-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 ResearchConceptsIdiopathic 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 mouseGene 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 microarraysInhibition and Role of let-7d in Idiopathic Pulmonary Fibrosis
Pandit KV, Corcoran D, Yousef H, Yarlagadda M, Tzouvelekis A, Gibson KF, Konishi K, Yousem SA, Singh M, Handley D, Richards T, Selman M, Watkins SC, Pardo A, Ben-Yehudah A, Bouros D, Eickelberg O, Ray P, Benos PV, Kaminski N. Inhibition and Role of let-7d in Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2010, 182: 220-229. PMID: 20395557, PMCID: PMC2913236, DOI: 10.1164/rccm.200911-1698oc.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCadherinsCells, CulturedDown-RegulationEpithelial CellsHMGA2 ProteinHumansIdiopathic Pulmonary FibrosisIn Situ HybridizationLungMiceMice, Inbred C57BLMicroRNAsPolymerase Chain ReactionPulmonary AlveoliS100 Calcium-Binding Protein A4S100 ProteinsSmad3 ProteinTransforming Growth Factor betaVimentinConceptsIdiopathic pulmonary fibrosisReal-time polymerase chain reactionQuantitative real-time polymerase chain reactionAlveolar epithelial cellsIPF lungsPulmonary fibrosisPolymerase chain reactionLet-7dEpithelial cellsLethal fibrotic lung diseaseAlpha-smooth muscle actinAlveolar septal thickeningMesenchymal markers N-cadherinFibrotic lung diseaseChain reactionLet-7d expressionSeptal thickeningPulmonary functionLung diseaseLung fibrosisEpithelial cell lineIntratracheal administrationIPF tissueProfibrotic effectsClinical trials
2024
SDePER: a hybrid machine learning and regression method for cell-type deconvolution of spatial barcoding-based transcriptomic data
Liu Y, Li N, Qi J, Xu G, Zhao J, Wang N, Huang X, Jiang W, Wei H, Justet A, Adams T, Homer R, Amei A, Rosas I, Kaminski N, Wang Z, Yan X. SDePER: a hybrid machine learning and regression method for cell-type deconvolution of spatial barcoding-based transcriptomic data. Genome Biology 2024, 25: 271. PMID: 39402626, PMCID: PMC11475911, DOI: 10.1186/s13059-024-03416-2.Peer-Reviewed Original ResearchNoninvasive 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
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 kinaseVISTA (PD-1H) Is a Crucial Immune Regulator to Limit Pulmonary Fibrosis.
Kim S, Adams T, Hu Q, Shin H, Chae G, Lee S, Sharma L, Kwon H, Lee F, Park H, Huh W, Manning E, Kaminski N, Sauler M, Chen L, Song J, Kim T, Kang M. VISTA (PD-1H) Is a Crucial Immune Regulator to Limit Pulmonary Fibrosis. American Journal Of Respiratory Cell And Molecular Biology 2023, 69: 22-33. PMID: 36450109, PMCID: PMC10324045, DOI: 10.1165/rcmb.2022-0219oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisImmune regulatorsTherapeutic potentialHuman idiopathic pulmonary fibrosisCrucial immune regulatorsNovel immune regulatorPulmonary fibrosis micePulmonary fibrosis modelNovel therapeutic targetRole of VISTAWild-type littermatesMonocyte-derived macrophagesT lymphocyte lineageVISTA expressionIPF treatmentAntibody treatmentImmune landscapeFibrotic mediatorsLung fibrosisFibrosis miceInflammatory responseFibrosis modelMyeloid populationsTherapeutic targetVascular-Parenchymal Cross-Talk Promotes Lung Fibrosis through BMPR2 Signaling.
Yanagihara T, Tsubouchi K, Zhou Q, Chong M, Otsubo K, Isshiki T, Schupp J, Sato S, Scallan C, Upagupta C, Revill S, Ayoub A, Chong S, Dvorkin-Gheva A, Kaminski N, Tikkanen J, Keshavjee S, Paré G, Guignabert C, Ask K, Kolb M. Vascular-Parenchymal Cross-Talk Promotes Lung Fibrosis through BMPR2 Signaling. American Journal Of Respiratory And Critical Care Medicine 2023, 207: 1498-1514. PMID: 36917778, DOI: 10.1164/rccm.202109-2174oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisVascular smooth muscle cellsAdvanced idiopathic pulmonary fibrosisPulmonary hypertensionFibrotic lungsVascular remodelingEndothelial cellsPulmonary fibrosisLung diseaseLung fibrosisDevelopment of PHConcomitant pulmonary hypertensionProgressive lung scarringPulmonary vascular remodelingFibrotic lung diseaseProgression of fibrosisActivation of VSMCsActive TGF-β1Fatal lung diseaseSmooth muscle cellsWhole-exome sequencingLung scarringEndothelial dysfunctionPoor prognosisFibrogenic effectsThyroid hormone modulates hyperoxic neonatal lung injury and mitochondrial function
Vamesu B, Nicola T, Li R, Hazra S, Matalon S, Kaminski N, Ambalavanan N, Kandasamy J. Thyroid hormone modulates hyperoxic neonatal lung injury and mitochondrial function. JCI Insight 2023, 8: e160697. PMID: 36917181, PMCID: PMC10243814, DOI: 10.1172/jci.insight.160697.Peer-Reviewed Original ResearchConceptsUmbilical cord-derived mesenchymal stem cellsNeonatal lung injuryMild bronchopulmonary dysplasiaSevere bronchopulmonary dysplasiaBronchopulmonary dysplasiaLung injuryELBW infantsThyroid hormonesLung homogenatesMitochondrial dysfunctionTotal T4Newborn miceLow birth weight infantsMitochondrial functionNeonatal hyperoxic lung injuryPeroxisome proliferator-activated receptor γ coactivator 1αProliferator-activated receptor γ coactivator 1αHyperoxic lung injuryReceptor γ coactivator 1αLow total T4Murine lung fibroblastsΓ coactivator 1αNeonatal hypothyroxinemiaWeight infantsPulmonary fibrosis
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 efficacyAirway basal cells show a dedifferentiated KRT17highPhenotype and promote fibrosis in idiopathic pulmonary fibrosis
Jaeger B, Schupp JC, Plappert L, Terwolbeck O, Artysh N, Kayser G, Engelhard P, Adams TS, Zweigerdt R, Kempf H, Lienenklaus S, Garrels W, Nazarenko I, Jonigk D, Wygrecka M, Klatt D, Schambach A, Kaminski N, Prasse A. Airway basal cells show a dedifferentiated KRT17highPhenotype and promote fibrosis in idiopathic pulmonary fibrosis. Nature Communications 2022, 13: 5637. PMID: 36163190, PMCID: PMC9513076, DOI: 10.1038/s41467-022-33193-0.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisAirway basal cellsPulmonary fibrosisNovel mouse xenograft modelEffect of saracatinibBasal cellsLimited treatment optionsMouse xenograft modelLung developmental processesConnectivity Map analysisExtracellular matrix depositionIPF lungsBronchial brushSevere fibrosisTreatment optionsBronchial brushingsNRG miceHealthy volunteersXenograft modelCyst-like structuresProfibrotic changesAlveolar compartmentFatal diseaseFibrosisPotent Src inhibitorCINS: Cell Interaction Network inference from Single cell expression data
Yuan Y, Cosme C, Adams TS, Schupp J, Sakamoto K, Xylourgidis N, Ruffalo M, Li J, Kaminski N, Bar-Joseph Z. CINS: Cell Interaction Network inference from Single cell expression data. PLOS Computational Biology 2022, 18: e1010468. PMID: 36095011, PMCID: PMC9499239, DOI: 10.1371/journal.pcbi.1010468.Peer-Reviewed Original ResearchConceptsCell type interactionsSingle-cell expression dataSingle-cell RNA-seq dataRNA-seq dataScRNA-seq experimentsCell-cell interactionsExpression dataCell typesMouse datasetsNetwork inferenceCell interactionsInteraction predictionNetwork analysisInference pipelineGenesCINSProteinInteractionBayesian network analysisCD38 Mediates Lung Fibrosis by Promoting Alveolar Epithelial Cell Aging.
Cui H, Xie N, Banerjee S, Dey T, Liu RM, Antony VB, Sanders YY, Adams TS, Gomez JL, Thannickal VJ, Kaminski N, Liu G. CD38 Mediates Lung Fibrosis by Promoting Alveolar Epithelial Cell Aging. American Journal Of Respiratory And Critical Care Medicine 2022, 206: 459-475. PMID: 35687485, DOI: 10.1164/rccm.202109-2151oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisLung fibrosisCD38 expressionAlveolar epithelial cell injuryEpithelial cell injuryEffective therapeutic strategyHuman lung parenchymaIPF lungsLung functionPulmonary fibrosisDisease progressionFibrotic lungsReal-time PCRYoung miceLung parenchymaOld miceCell injuryTherapeutic strategiesFibrosisPharmacological inactivationCD38Single-cell RNA sequencingFlow cytometryWestern blottingOld animalsMicroenvironmental 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 forcesCharacterization 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
Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis
Chandran RR, Xie Y, Gallardo-Vara E, Adams T, Garcia-Milian R, Kabir I, Sheikh AQ, Kaminski N, Martin KA, Herzog EL, Greif DM. Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis. Nature Communications 2021, 12: 7179. PMID: 34893592, PMCID: PMC8664937, DOI: 10.1038/s41467-021-27499-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationDisease Models, AnimalDown-RegulationExtracellular MatrixFemaleFibroblastsFibrosisHumansKruppel-Like Factor 4LungLung InjuryMaleMesenchymal Stem CellsMiceMice, Inbred C57BLMyofibroblastsReceptor, Platelet-Derived Growth Factor betaRespiratory Tract DiseasesSignal TransductionTransforming Growth Factor betaConceptsMesenchymal cell typesPlatelet-derived growth factor receptorSmooth muscle actinLung fibrosisKruppel-like factor 4Forkhead box M1Growth factor receptorCell transitionCell typesExtracellular matrixDistinct rolesKLF4Box M1C chemokine ligandMesenchymal cell subtypesFactor receptorPro-fibrotic effectsFactor 4PDGFRMesenchymeCellsMacrophage accumulationKLF4 levelsChemokine ligandLung fibrogenesisFibroblasts positive for meflin have anti-fibrotic properties in pulmonary fibrosis
Nakahara Y, Hashimoto N, Sakamoto K, Enomoto A, Adams TS, Yokoi T, Omote N, Poli S, Ando A, Wakahara K, Suzuki A, Inoue M, Hara A, Mizutani Y, Imaizumi K, Kawabe T, Rosas IO, Takahashi M, Kaminski N, Hasegawa Y. Fibroblasts positive for meflin have anti-fibrotic properties in pulmonary fibrosis. European Respiratory Journal 2021, 58: 2003397. PMID: 34049947, DOI: 10.1183/13993003.03397-2020.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisAnti-fibrotic propertiesRole of fibroblastsFibroblastic fociPathogenesis of IPFLung fibrosis modelSenescence-associated secretory phenotypeNormal lung samplesMesenchymal stromal cellsIPF patientsIPF lungsDense fibrosisPathological hallmark lesionsFibrosis modelFibrotic lungsHallmark lesionsSingle-cell atlasActive fibrogenesisElderly individualsLung samplesFibrosisSingle-cell RNA sequencingFibrotic regionsSecretory phenotypeElevated IL-15 concentrations in the sarcoidosis lung are independent of granuloma burden and disease phenotypes
Minasyan M, Sharma L, Pivarnik T, Liu W, Adams T, Bermejo S, Peng X, Liu A, Ishikawa G, Perry C, Kaminski N, Gulati M, Herzog EL, Dela Cruz CS, Ryu C. Elevated IL-15 concentrations in the sarcoidosis lung are independent of granuloma burden and disease phenotypes. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2021, 320: l1137-l1146. PMID: 33851886, PMCID: PMC8285626, DOI: 10.1152/ajplung.00575.2020.Peer-Reviewed Original ResearchConceptsIL-15 concentrationsIL-15Bronchoalveolar lavageDisease pathogenesisSarcoidosis lungClinical manifestationsLineages of miceIL-15 receptor αHuman cohortsInflammation of sarcoidosisIL-15 levelsOngoing inflammatory processSystemic granulomatous diseaseNumber of granulomasDisease phenotypeSarcoidosis cohortTDM administrationGranuloma numberComorbid conditionsClinical progressionInterleukin-15Granulomatous diseaseInflammatory processGranuloma formationHealthy controls