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 ResearchMeSH KeywordsAnimalsBiomarkersBleomycinDisease Models, AnimalFemaleHumansIdiopathic Pulmonary FibrosisLungMacrophagesMaleMiceMice, Inbred C57BLPneumoniaPositron-Emission TomographyPulmonary FibrosisConceptsIdiopathic 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
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
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 ResearchMeSH KeywordsAnimalsBleomycinFibroblastsFibrosisHumansIdiopathic Pulmonary FibrosisLungMiceProtein Kinase InhibitorsSrc-Family KinasesTransforming Growth Factor betaConceptsIdiopathic 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 efficacyA 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
2020
Single-cell RNA-seq reveals ectopic and aberrant lung-resident cell populations in idiopathic pulmonary fibrosis
Adams TS, Schupp JC, Poli S, Ayaub EA, Neumark N, Ahangari F, Chu SG, Raby BA, DeIuliis G, Januszyk M, Duan Q, Arnett HA, Siddiqui A, Washko GR, Homer R, Yan X, Rosas IO, Kaminski N. Single-cell RNA-seq reveals ectopic and aberrant lung-resident cell populations in idiopathic pulmonary fibrosis. Science Advances 2020, 6: eaba1983. PMID: 32832599, PMCID: PMC7439502, DOI: 10.1126/sciadv.aba1983.Peer-Reviewed Original ResearchMeSH KeywordsEndothelial CellsHumansIdiopathic Pulmonary FibrosisLungPulmonary Disease, Chronic ObstructiveRNA-SeqConceptsIdiopathic pulmonary fibrosisVascular endothelial cellsIPF lungsPulmonary fibrosisChronic obstructive pulmonary disease (COPD) lungsFatal interstitial lung diseaseEndothelial cellsInterstitial lung diseaseCell populationsIPF myofibroblastsMyofibroblast fociNonsmoker controlsLung diseaseCOPD lungsBasaloid cellsSingle-cell atlasInvasive fibroblastsMacrophage populationsLungStromal cellsEpithelial cellsFibrosisCellular populationsDevelopmental markersSingle-cell RNA-seq
2019
Transcriptional regulatory model of fibrosis progression in the human lung
McDonough JE, Ahangari F, Li Q, Jain S, Verleden SE, Herazo-Maya J, Vukmirovic M, DeIuliis G, Tzouvelekis A, Tanabe N, Chu F, Yan X, Verschakelen J, Homer RJ, Manatakis DV, Zhang J, Ding J, Maes K, De Sadeleer L, Vos R, Neyrinck A, Benos PV, Bar-Joseph Z, Tantin D, Hogg JC, Vanaudenaerde BM, Wuyts WA, Kaminski N. Transcriptional regulatory model of fibrosis progression in the human lung. JCI Insight 2019, 4 PMID: 31600171, PMCID: PMC6948862, DOI: 10.1172/jci.insight.131597.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisAdvanced fibrosisAlveolar surface densityFibrosis progressionLung fibrosisHuman lungDynamic Regulatory Events MinerExtent of fibrosisIPF lungsPulmonary fibrosisControl lungsIPF tissueB lymphocytesFibrosisLungLinear mixed-effects modelsMixed-effects modelsGene expression changesSystems biology modelsDifferential gene expression analysisGene expression analysisProgressionGene expression networksRNA sequencingBiology models
2018
A role for telomere length and chromosomal damage in idiopathic pulmonary fibrosis
McDonough JE, Martens DS, Tanabe N, Ahangari F, Verleden SE, Maes K, Verleden GM, Kaminski N, Hogg JC, Nawrot TS, Wuyts WA, Vanaudenaerde BM. A role for telomere length and chromosomal damage in idiopathic pulmonary fibrosis. Respiratory Research 2018, 19: 132. PMID: 29986708, PMCID: PMC6038197, DOI: 10.1186/s12931-018-0838-4.Peer-Reviewed Original ResearchMeSH KeywordsAgedChromosome AberrationsDNA DamageFemaleHumansIdiopathic Pulmonary FibrosisMaleMiddle AgedTelomereTelomere ShorteningX-Ray MicrotomographyConceptsIPF lungsDisease severityChromosomal damagePulmonary fibrosisTelomere lengthBackgroundIdiopathic pulmonary fibrosisRegional disease severityStructural disease severityIdiopathic pulmonary fibrosisFatal lung diseaseAirway epithelial cellsMultivariate linear mixed-effects modelDonor lungsFibroblastic fociLung diseaseFibrotic markersTransplant surgeryPathological changesSevere diseaseLungLinear mixed-effects modelsQuantitative histologyMixed-effects modelsExtracellular matrixSeverity
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