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
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 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
2021
Integrated Single-Cell Atlas of Endothelial Cells of the Human Lung
Schupp JC, Adams TS, Cosme C, Raredon MSB, Yuan Y, Omote N, Poli S, Chioccioli M, Rose KA, Manning EP, Sauler M, DeIuliis G, Ahangari F, Neumark N, Habermann AC, Gutierrez AJ, Bui LT, Lafyatis R, Pierce RW, Meyer KB, Nawijn MC, Teichmann SA, Banovich NE, Kropski JA, Niklason LE, Pe’er D, Yan X, Homer RJ, Rosas IO, Kaminski N. Integrated Single-Cell Atlas of Endothelial Cells of the Human Lung. Circulation 2021, 144: 286-302. PMID: 34030460, PMCID: PMC8300155, DOI: 10.1161/circulationaha.120.052318.Peer-Reviewed Original ResearchConceptsDifferential expression analysisPrimary lung endothelial cellsLung endothelial cellsCell typesMarker genesExpression analysisSingle-cell RNA sequencing dataCross-species analysisVenous endothelial cellsEndothelial marker genesSingle-cell atlasMarker gene setsRNA sequencing dataEndothelial cellsSubsequent differential expression analysisDifferent lung cell typesResident cell typesLung cell typesCellular diversityEndothelial cell typesCapillary endothelial cellsHuman lung endothelial cellsPhenotypic diversityEndothelial diversityIndistinguishable populations
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 ResearchConceptsIdiopathic 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-seqReconstructed Single-Cell Fate Trajectories Define Lineage Plasticity Windows during Differentiation of Human PSC-Derived Distal Lung Progenitors
Hurley K, Ding J, Villacorta-Martin C, Herriges MJ, Jacob A, Vedaie M, Alysandratos KD, Sun YL, Lin C, Werder RB, Huang J, Wilson AA, Mithal A, Mostoslavsky G, Oglesby I, Caballero IS, Guttentag SH, Ahangari F, Kaminski N, Rodriguez-Fraticelli A, Camargo F, Bar-Joseph Z, Kotton DN. Reconstructed Single-Cell Fate Trajectories Define Lineage Plasticity Windows during Differentiation of Human PSC-Derived Distal Lung Progenitors. Cell Stem Cell 2020, 26: 593-608.e8. PMID: 32004478, PMCID: PMC7469703, DOI: 10.1016/j.stem.2019.12.009.Peer-Reviewed Original ResearchConceptsPluripotent stem cellsHuman pluripotent stem cellsLung progenitorsSingle-cell RNACell fate trajectoriesDistal lung progenitorsEndodermal fateLentiviral barcodingSelf-renewal capacityDevelopmental plasticityWnt responseNKX2-1Stem cellsStable phenotypeAlveolar epithelial type 2 cellsProgenitorsFacultative progenitorsPlasticity windowContinuous state Hidden Markov ModelsEpithelial type 2 cellsDifferentiationFateAEC2sType 2 cellsBarcoding
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 modelsIntegrating multiomics longitudinal data to reconstruct networks underlying lung development
Ding J, Ahangari F, Espinoza CR, Chhabra D, Nicola T, Yan X, Lal CV, Hagood JS, Kaminski N, Bar-Joseph Z, Ambalavanan N. Integrating multiomics longitudinal data to reconstruct networks underlying lung development. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2019, 317: l556-l568. PMID: 31432713, PMCID: PMC6879899, DOI: 10.1152/ajplung.00554.2018.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornChildChild, PreschoolDNA MethylationEpigenesis, GeneticFemaleGene Expression ProfilingGene Expression Regulation, DevelopmentalGene Regulatory NetworksHigh-Throughput Nucleotide SequencingHumansImmunity, InnateInfantInfant, NewbornLungMaleMiceMice, Inbred C57BLMicroRNAsOrganogenesisProteomicsPulmonary AlveoliRNA, MessengerSingle-Cell AnalysisTranscriptomeConceptsSingle-cell RNA-seq dataLung developmentDynamic regulatory networksOmics data setsRNA-seq dataIndividual cell typesHuman lung developmentRegulatory networksDNA methylationLaser capture microdissectionEpigenetic changesExpression trajectoriesKey pathwaysCell typesActive pathwaysCapture microdissectionRegulatorKey eventsInnate immunityNew insightsSpecific key eventsPathwayComprehensive understandingProteomicsMethylation
2013
VEGF controls lung Th2 inflammation via the miR-1–Mpl (myeloproliferative leukemia virus oncogene)–P-selectin axis
Takyar S, Vasavada H, Zhang JG, Ahangari F, Niu N, Liu Q, Lee CG, Cohn L, Elias JA. VEGF controls lung Th2 inflammation via the miR-1–Mpl (myeloproliferative leukemia virus oncogene)–P-selectin axis. Journal Of Experimental Medicine 2013, 210: 1993-2010. PMID: 24043765, PMCID: PMC3782056, DOI: 10.1084/jem.20121200.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factorTh2 inflammationLung endotheliumMiR-1Th2-mediated lung inflammationIL-13 overexpressionLung-specific overexpressionHouse dust mitePotential therapeutic targetEndothelial growth factorMiR-1 expressionLung inflammationInflammatory disordersDust miteInflammation modelInflammatory responseIntranasal deliveryRole of microRNAsTherapeutic targetInflammationP-selectinGrowth factorVivo knockdownEffector pathwaysEndothelium