2025
Epigenetic age acceleration in idiopathic pulmonary fibrosis revealed by DNA methylation clocks
Kurbanov D, Ahangari F, Adams T, De Man R, Tang J, Carlon M, Abu Hussein N, Cortesi E, Zapata M, De Sadelaar L, Wuyts W, Vanaudenaerde B, Kaminski N, McDonough J. Epigenetic age acceleration in idiopathic pulmonary fibrosis revealed by DNA methylation clocks. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2025, 328: l456-l462. PMID: 39970931, DOI: 10.1152/ajplung.00171.2024.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisIdiopathic pulmonary fibrosis tissuePulmonary fibrosisLung tissueEpigenetic clocksPotential of DNA methylationDNA methylation levelsDebilitating lung diseaseIllumina MethylationEPIC arrayHuman lung tissueEpigenetic ageDNA methylation clocksBiological ageAffected lung tissueIPF casesClinical prognosisMethylation patternsDNA methylationLung diseaseHealthy controlsAcceleration of biological agingMethylation levelsMethylationEPIC arrayAge accelerationClinical assessmentCD103+ dendritic cell — fibroblast crosstalk via TLR9, TDO2, and AHR signaling drives lung fibrogenesis
Carter H, Costa R, Adams T, Gilchrist T, Emch C, Bame M, Oldham J, Huang S, Linderholm A, Noth I, Kaminski N, Moore B, Gurczynski S. CD103+ dendritic cell — fibroblast crosstalk via TLR9, TDO2, and AHR signaling drives lung fibrogenesis. JCI Insight 2025, 10 PMID: 39964756, PMCID: PMC11949071, DOI: 10.1172/jci.insight.177072.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDBasic Helix-Loop-Helix Transcription FactorsBleomycinDendritic CellsDisease Models, AnimalFibroblastsHumansIdiopathic Pulmonary FibrosisIntegrin alpha ChainsInterleukin-6LungMaleMiceMice, Inbred C57BLReceptors, Aryl HydrocarbonSignal TransductionToll-Like Receptor 9Tryptophan OxygenaseConceptsIdiopathic pulmonary fibrosisAhR signalingMice treated with BLMIL-17+ cellsCD103+ DCLoss of lung functionStudies of human samplesLimited treatment optionsTreated ex vivoProduction of IL-6Inflammatory cytokine productionExon 2 deletionExpression of TDO2IL-6 productionAdoptive transferCD11c-CreCD11c+ cellsImmunological changesPulmonary fibrosisTLR agonistsProgressive scarringTreatment optionsCytokine productionLung fibrogenesisAryl hydrocarbon receptor
2024
SINGLE-CELL ANALYSIS OF SOMATIC MUTATIONS IN HUMAN LUNG REVEALS ASSOCIATION WITH TRANSCRIPTIONAL CHANGES IN AGING
De Man R, Adams T, McDonough J, Cala-Garcia J, Moss B, Yan X, Rosas I, Kaminski N. SINGLE-CELL ANALYSIS OF SOMATIC MUTATIONS IN HUMAN LUNG REVEALS ASSOCIATION WITH TRANSCRIPTIONAL CHANGES IN AGING. Innovation In Aging 2024, 8: 571-572. PMCID: PMC11690935, DOI: 10.1093/geroni/igae098.1872.Peer-Reviewed Original ResearchSomatic mutationsMutational burdenCell type annotationAlveolar type 1DNA damage response genesAnalysis of somatic mutationsSomatic mutation accumulationAccumulation of somatic mutationsCell typesUbiquitin ligase geneDamage response genesLoss of cell functionAnalyzed somatic mutationsDecreased expressionSingle-cell RNAseqLigase geneMutation accumulationTop genesSignaling genesCell marker genesResponse genesTranscriptional changesAlveolar type 1 cellsGenesMarker genesPredicting lung aging using scRNA-Seq data
Song Q, Singh A, McDonough J, Adams T, Vos R, De Man R, Myers G, Ceulemans L, Vanaudenaerde B, Wuyts W, Yan X, Schupp J, Hagood J, Kaminski N, Bar-Joseph Z. Predicting lung aging using scRNA-Seq data. PLOS Computational Biology 2024, 20: e1012632. PMID: 39700255, PMCID: PMC11741621, DOI: 10.1371/journal.pcbi.1012632.Peer-Reviewed Original ResearchSDePER: 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 ResearchIdentification 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 fibrosisApplying single-cell profiling to assess drug anti-fibrotic properties in the human precision-cut lung slice model of fibrosis
Justet A, Mitash M, Raredon S, Pineda R, Adams T, Al Hussein N, Ishizuka M, Hahram K, Khoury J, Ahangari F, Xiting Y, Naftali K, Melanie K. Applying single-cell profiling to assess drug anti-fibrotic properties in the human precision-cut lung slice model of fibrosis. 2024, oa1896. DOI: 10.1183/13993003.congress-2024.oa1896.Peer-Reviewed Original ResearchPlasma collagen neoepitopes are associated with multiorgan disease in the ACCESS and GRADS sarcoidosis cohorts
Sand J, Jessen H, Leeming D, Yu S, Lee C, Hu B, Sun Y, Adams T, Pivarnik T, Liu A, Woo S, McGovern J, Fiorini V, Saber T, Higuero-Sevilla J, Gulati M, Kaminski N, Damsky W, Shaw A, Mohanty S, Goobie G, Zhang Y, Herzog E, Ryu C. Plasma collagen neoepitopes are associated with multiorgan disease in the ACCESS and GRADS sarcoidosis cohorts. Thorax 2024, 79: 1136-1144. PMID: 39117421, DOI: 10.1136/thorax-2023-221095.Peer-Reviewed Original ResearchSarcoidosis cohortMultiorgan diseasePRO-C3Interleukin-4Case Control Etiologic Study of SarcoidosisPlasma levels of interleukin-4Alpha-1 antitrypsin deficiencyLevels of interleukin-4Pathogenesis of sarcoidosisC6MC3MHealthy control patientsStudy of sarcoidosisGenomic researchAbnormal extracellular matrixAssociated with dermatological diseaseCollagen degradationScadding stageCorticosteroid useComplex diseasesPRO-C6Control patientsIL-13IL-5IL-9Single-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 regionsDendritic Cell - Fibroblast Crosstalk Via Toll-like Receptor 9 and Aryl Hyrdocarbon Receptor Signaling Drives Lung Fibrogenesis
Carter H, Costa R, Adams T, Moore B, Kaminski N, Gurczynski S. Dendritic Cell - Fibroblast Crosstalk Via Toll-like Receptor 9 and Aryl Hyrdocarbon Receptor Signaling Drives Lung Fibrogenesis. 2024, a5207-a5207. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a5207.Peer-Reviewed Original ResearchProfibrotic Role of GPR87 in Pulmonary Fibrosis
Khoury J, Ahangari F, Manning E, Justet A, barnthaler T, Adams T, Necola F, Alysandratos K, Beermann M, Kotton D, Kaminski N. Profibrotic Role of GPR87 in Pulmonary Fibrosis. 2024, a5183-a5183. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a5183.Peer-Reviewed Original ResearchIPF Aberrant Basaloid Cells Have Chromatin Accessibility Features Distinct From Other Lung Epithelial Cells
Adams T, Schupp J, Balayev A, Justet A, Sharma P, Anderson S, Nekola F, Deiuliis G, Yan X, Wuyts W, Vanaudenaerde B, Kaminski N. IPF Aberrant Basaloid Cells Have Chromatin Accessibility Features Distinct From Other Lung Epithelial Cells. 2024, a4898-a4898. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a4898.Peer-Reviewed Original ResearchApplying Single Cell Profiling to Assess Drug Anti Fibrotic Properties in the Human Precision Cut Lung Slice Model of Fibrosis
Justet A, Mitash N, Pineda R, Adams T, Balayev A, Abu Hussein N, Ishizuka M, Kim H, Khoury J, Ahangari F, Yan X, Kaminski N, Koenigshoff M. Applying Single Cell Profiling to Assess Drug Anti Fibrotic Properties in the Human Precision Cut Lung Slice Model of Fibrosis. 2024, a4906-a4906. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a4906.Peer-Reviewed Original ResearchCFTR Modulators Reprogram Sex-Specific Airway Neutrophil Signaling
Yin H, Kockar Kizilirmak T, Li N, Adams T, Sauler M, Gomez J, Britto-Leon C. CFTR Modulators Reprogram Sex-Specific Airway Neutrophil Signaling. 2024, a7454-a7454. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a7454.Peer-Reviewed Original ResearchDedifferentiated early postnatal lung myofibroblasts redifferentiate in adult disease
Chandran R, Adams T, Kabir I, Gallardo-Vara E, Kaminski N, Gomperts B, Greif D. Dedifferentiated early postnatal lung myofibroblasts redifferentiate in adult disease. Frontiers In Cell And Developmental Biology 2024, 12: 1335061. PMID: 38572485, PMCID: PMC10987733, DOI: 10.3389/fcell.2024.1335061.Peer-Reviewed Original ResearchRNA sequencing analysisSMA+ myofibroblastsGene expression profilesLung myofibroblastsAdult lungSequence analysisResponse to lung injurySingle cell RNA sequencing analysisTissue remodeling genesSmooth muscle cell markersLung to hypoxiaExpression profilesRemodeling genesMuscle cell markersResponse to injuryCell typesSMA cellsLineage tracingLung injuryCell markersLineagesGenesAdult diseaseDrug bleomycinLung surface areaFibrotic 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-GarcĂa 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 markersSingle-cell transcriptomic analysis of human pleura reveals stromal heterogeneity and informs in vitro models of mesothelioma
Obacz J, Valer J, Nibhani R, Adams T, Schupp J, Veale N, Lewis-Wade A, Flint J, Hogan J, Aresu G, Coonar A, Peryt A, Biffi G, Kaminski N, Francies H, Rassl D, Garnett M, Rintoul R, Marciniak S. Single-cell transcriptomic analysis of human pleura reveals stromal heterogeneity and informs in vitro models of mesothelioma. European Respiratory Journal 2024, 63: 2300143. PMID: 38212075, PMCID: PMC10809128, DOI: 10.1183/13993003.00143-2023.Peer-Reviewed Original ResearchConceptsSingle-cell transcriptome atlasSingle-cell levelSingle-cell transcriptome analysisTranscriptome dataTranscriptomic atlasTranscriptomic characterisationMesothelial cellsCell atlasDevelopment of targeted therapiesMalignant mesothelial cellsModel of mesotheliomaUniversal fibroblastsIn vitro modelMast-cell expressed membrane protein-1 is expressed in classical monocytes and alveolar macrophages in idiopathic pulmonary fibrosis and regulates cell chemotaxis, adhesion, and migration in a TGFβ-dependent manner
Perrot C, Karampitsakos T, Unterman A, Adams T, Marlin K, Arsenault A, Zhao A, Kaminski N, Katlaps G, Patel K, Bandyopadhyay D, Herazo-Maya J. Mast-cell expressed membrane protein-1 is expressed in classical monocytes and alveolar macrophages in idiopathic pulmonary fibrosis and regulates cell chemotaxis, adhesion, and migration in a TGFβ-dependent manner. American Journal Of Physiology - Cell Physiology 2024, 326: c964-c977. PMID: 38189137, PMCID: PMC11193480, DOI: 10.1152/ajpcell.00563.2023.Peer-Reviewed Original Research
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 population
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