2024
Identification of FGFR4 as a regulator of myofibroblast differentiation in pulmonary fibrosis
Ghanem M, Justet A, Jaillet M, Vasarmidi E, Boghanim T, Hachem M, Vadel A, Joannes A, Mordant P, Balayev A, Adams T, Mal H, Cazes A, Poté N, Mailleux A, Crestani B. Identification of FGFR4 as a regulator of myofibroblast differentiation in pulmonary fibrosis. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2024, 327: l818-l830. PMID: 39350729, DOI: 10.1152/ajplung.00184.2023.Peer-Reviewed Original ResearchWild type littermatesFibroblast growth factorMurine embryonic fibroblastsEndothelin-1Pulmonary fibrosisFGFR4 inhibitionBleomycin-induced pulmonary fibrosisIn vitroMyofibroblast differentiationBleomycin-induced lung fibrosisPulmonary fibrosis in vivoTGF-bLung fibroblastsPro-fibrotic propertiesProtein levelsIn vivoAnti-fibrotic propertiesFibrosis in vivoRegulation of myofibroblast differentiationDevelopment of bleomycin-induced lung fibrosisWT miceTherapeutic optionsHuman lung fibroblastsIPF lungsLung fibrosisSingle-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis.
Zhao A, Unterman A, Abu Hussein N, Sharma P, Nikola F, Flint J, Yan X, Adams T, Justet A, Sumida T, Zhao J, Schupp J, Raredon M, Ahangari F, Deluliis G, Zhang Y, Buendia-Roldan I, Adegunsoye A, Sperling A, Prasse A, Ryu C, Herzog E, Selman M, Pardo A, Kaminski N. Single-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis. American Journal Of Respiratory And Critical Care Medicine 2024, 210: 1252-1266. PMID: 38924775, PMCID: PMC11568434, DOI: 10.1164/rccm.202401-0078oc.Peer-Reviewed Original ResearchFibrotic hypersensitivity pneumonitisIdiopathic pulmonary fibrosisPeripheral blood mononuclear cellsBronchoalveolar lavage cellsBlood mononuclear cellsClassical monocytesHypersensitivity pneumonitisPulmonary fibrosisT cellsImmune perturbationsLavage cellsMononuclear cellsCD8+ T cellsCytotoxic T cellsInterstitial lung diseaseHypersensitivity pneumonitis patientsCytotoxic CD4Immune aberrationsPneumonic patientsPneumonitisLung diseaseHealthy controlsImmune mechanismsPatient cellsSingle-cell transcriptomicsNoninvasive 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 regionsFibrotic cocktail treated human precision lung slices replicate the cellular diversity of the IPF lung
Justet A, Pineda H, Adams T, Balayev A, Mitash N, Ishizuka M, Kim H, Khoury J, Cala-García J, Flint J, Schupp J, Ahangari F, Yan X, Rosas I, Kaminski N, Königshoff M. Fibrotic cocktail treated human precision lung slices replicate the cellular diversity of the IPF lung. Revue Des Maladies Respiratoires 2024, 41: 218. DOI: 10.1016/j.rmr.2024.01.074.Peer-Reviewed Original ResearchCellular repertoireCell typesSingle cell platformsSequence readsCDNA libraryIllumina platformHuman genomeNucleus transcriptomicsCellular diversityIPF lungsPulmonary fibrosisEMT markersAirway epithelial cellsBasaloid cellsCellular populationsEpithelial cellsFibrotic fibroblastsCell platformLung slicesLung cell populationsHuman precision-cut lung slicesCell populationsSenescence markersCellsBasal markers
2023
Circulating Mitochondrial DNA Is Associated With High Levels of Fatigue in Two Independent Sarcoidosis Cohorts
Fiorini V, Hu B, Sun Y, Yu S, McGovern J, Gandhi S, Woo S, Turcotte-Foster S, Pivarnik T, Khan Z, Adams T, Herzog E, Kaminski N, Gulati M, Ryu C. Circulating Mitochondrial DNA Is Associated With High Levels of Fatigue in Two Independent Sarcoidosis Cohorts. CHEST Journal 2023, 165: 1174-1185. PMID: 37977267, PMCID: PMC11110677, DOI: 10.1016/j.chest.2023.11.020.Peer-Reviewed Original ResearchPatient-related outcome measuresToll-like receptor 9Fatigue Assessment ScalePlasma mtDNA concentrationsTLR9 activationSarcoidosis patientsMtDNA concentrationsMulti-organ sarcoidosisCommon chief complaintInnate immune activationNovel therapeutic strategiesDomains of fatigueSevere clinical phenotypePsychobiologic mechanismsSarcoidosis cohortScadding stageCorticosteroid useCytokine levelsExtrapulmonary diseaseProspective cohortFAS scoresPulmonary fibrosisChief complaintImmune activationPatient populationVISTA (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 targetmicroRNA-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 mouse
2022
Airway 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 inhibitorCD38 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 animalsLeveraging Cell-Specific Disease Signatures to Predict New Drug Therapies for Idiopathic Pulmonary Fibrosis
Adams T, Song Q, Justet A, Mcdonough J, DeIuliis G, Yan X, Bar-Joseph Z, Kaminski N. Leveraging Cell-Specific Disease Signatures to Predict New Drug Therapies for Idiopathic Pulmonary Fibrosis. 2022, a2318-a2318. DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2318.Peer-Reviewed Original Research
2021
Fibroblasts 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 phenotype
2016
P063 The Distribution and Efficacy of MiR-29 Mimicry as a Therapy for Pulmonary Fibrosis Induced by Bleomycin in Mice
Yu G, Wang R, Ibarra G, Tzouvelekis A, Woolard T, herazo-maya J, Sakamoto K, Li Q, Deluliis G, Ahnangari F, Vukmirovic M, Aurelien N, Adams T, Munivar A, Kaminski N. P063 The Distribution and Efficacy of MiR-29 Mimicry as a Therapy for Pulmonary Fibrosis Induced by Bleomycin in Mice. QJM 2016, 109: s42-s43. DOI: 10.1093/qjmed/hcw124.036.Peer-Reviewed Original ResearchPulmonary fibrosisFibrosis