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 programIntegrated 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 populationsThyroid 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 mouseSingle-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-seqGene 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 microarraysMMP1 and MMP7 as Potential Peripheral Blood Biomarkers in Idiopathic Pulmonary Fibrosis
Rosas IO, Richards TJ, Konishi K, Zhang Y, Gibson K, Lokshin AE, Lindell KO, Cisneros J, MacDonald SD, Pardo A, Sciurba F, Dauber J, Selman M, Gochuico BR, Kaminski N. MMP1 and MMP7 as Potential Peripheral Blood Biomarkers in Idiopathic Pulmonary Fibrosis. PLOS Medicine 2008, 5: e93. PMID: 18447576, PMCID: PMC2346504, DOI: 10.1371/journal.pmed.0050093.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisInterstitial lung diseaseSubclinical interstitial lung diseasePulmonary fibrosisLung diseaseIPF patientsChronic progressive fibrotic lung diseaseControl individualsAsymptomatic interstitial lung diseaseProgressive fibrotic lung diseaseChronic obstructive pulmonary diseasePotential peripheral blood biomarkerChronic hypersensitivity pneumonitisPeripheral blood biomarkersChronic lung diseaseObstructive pulmonary diseaseFibrotic lung diseaseBronchoalveolar lavage fluidIndependent validation cohortFamilial pulmonary fibrosisProtein signaturesPulmonary diseaseSubstantial morbidityHypersensitivity pneumonitisLavage fluidInhibition 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 regionsSingle-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 modelChallenges and Opportunities for Commercializing Technologies in the Pulmonary Arena: An Official American Thoracic Society Report
Vukmirovic M, Benam K, Rose J, Turner S, Magin C, Lagares D, Cohen A, Kaminski N, Hirota J, Maher T, Konigshoff M, Mallampalli R, Sheppard D, Tarran R, Gomer R, Kenyon N, Morris D, Hobbie S, Raju S, Petrache I, Watkins T, Kumar R, Lam W, Sherer T, Hecker L. Challenges and Opportunities for Commercializing Technologies in the Pulmonary Arena: An Official American Thoracic Society Report. Annals Of The American Thoracic Society 2024, 21: 1-11. PMID: 37903340, PMCID: PMC10867911, DOI: 10.1513/annalsats.202310-872st.Peer-Reviewed Original Research
2023
Somatic Mutations: The Next Frontier in Demystifying Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis?
Yan X, Kaminski N. Somatic Mutations: The Next Frontier in Demystifying Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis? American Journal Of Respiratory And Critical Care Medicine 2023, 208: 1150-1151. PMID: 37856835, PMCID: PMC10868359, DOI: 10.1164/rccm.202310-1774ed.Peer-Reviewed Original ResearchAlveolar Vascular Remodeling in Nonspecific Interstitial Pneumonia: Replacement of Normal Lung Capillaries with COL15A1-Positive Endothelial Cells.
Schupp J, Manning E, Chioccioli M, Kamp J, Christian L, Ryu C, Herzog E, Kühnel M, Prasse A, Kaminski N, Jonigk D, Homer R, Neubert L, Ius F, stringJustet A, Hariri L, Seeliger B, Welte T, Knipe R, Gottlieb J. Alveolar Vascular Remodeling in Nonspecific Interstitial Pneumonia: Replacement of Normal Lung Capillaries with COL15A1-Positive Endothelial Cells. American Journal Of Respiratory And Critical Care Medicine 2023, 208: 819-822. PMID: 37552025, PMCID: PMC10563189, DOI: 10.1164/rccm.202303-0544le.Peer-Reviewed Original ResearchSRC 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 kinaseWhen Development of the Alveolar Gas Exchange Unit Fails: Universal Single-Cell Lessons from Rare Monogenic Disorders
Schupp J, Kaminski N. When Development of the Alveolar Gas Exchange Unit Fails: Universal Single-Cell Lessons from Rare Monogenic Disorders. American Journal Of Respiratory And Critical Care Medicine 2023, 208: 652-654. PMID: 37555730, PMCID: PMC10515565, DOI: 10.1164/rccm.202307-1271ed.Commentaries, Editorials and LettersAn AI-powered patient triage platform for future viral outbreaks using COVID-19 as a disease model
Charkoftaki G, Aalizadeh R, Santos-Neto A, Tan W, Davidson E, Nikolopoulou V, Wang Y, Thompson B, Furnary T, Chen Y, Wunder E, Coppi A, Schulz W, Iwasaki A, Pierce R, Cruz C, Desir G, Kaminski N, Farhadian S, Veselkov K, Datta R, Campbell M, Thomaidis N, Ko A, Thompson D, Vasiliou V. An AI-powered patient triage platform for future viral outbreaks using COVID-19 as a disease model. Human Genomics 2023, 17: 80. PMID: 37641126, PMCID: PMC10463861, DOI: 10.1186/s40246-023-00521-4.Peer-Reviewed Original ResearchConceptsCOVID-19 patientsDisease severityViral outbreaksFuture viral outbreaksLength of hospitalizationIntensive care unitWorse disease prognosisLife-threatening illnessEffective medical interventionsCOVID-19Clinical decision treeGlucuronic acid metabolitesNew potential biomarkersHospitalization lengthCare unitComorbidity dataSerotonin levelsDisease progressionHealthy controlsPatient outcomesDisease prognosisPatient transferPatientsHealthcare resourcesPotential biomarkersiDESC: identifying differential expression in single-cell RNA sequencing data with multiple subjects
Liu Y, Zhao J, Adams T, Wang N, Schupp J, Wu W, McDonough J, Chupp G, Kaminski N, Wang Z, Yan X. iDESC: identifying differential expression in single-cell RNA sequencing data with multiple subjects. BMC Bioinformatics 2023, 24: 318. PMID: 37608264, PMCID: PMC10463720, DOI: 10.1186/s12859-023-05432-8.Peer-Reviewed Original ResearchIntegrative genetic and genomic networks identify microRNA associated with COPD and ILD
Pavel A, Garrison C, Luo L, Liu G, Taub D, Xiao J, Juan-Guardela B, Tedrow J, Alekseyev Y, Yang I, Geraci M, Sciurba F, Schwartz D, Kaminski N, Beane J, Spira A, Lenburg M, Campbell J. Integrative genetic and genomic networks identify microRNA associated with COPD and ILD. Scientific Reports 2023, 13: 13076. PMID: 37567908, PMCID: PMC10421936, DOI: 10.1038/s41598-023-39751-w.Peer-Reviewed Original ResearchConceptsSeed sequenceGene expressionShort RNA sequencingAirway differentiationIntegrative network analysisExpression networksRNA sequencingGenomic networksMiRNA regulatorsMiRNA isoformsNotch pathwayIsomiRsDistinct subclustersSNP microarraysGenesMicroRNAsMolecular heterogeneityILD pathogenesisDisease networkOverexpressionSequenceExpressionNetwork analysisDifferentiationGrb2A statistical framework to identify cell types whose genetically regulated proportions are associated with complex diseases
Liu W, Deng W, Chen M, Dong Z, Zhu B, Yu Z, Tang D, Sauler M, Lin C, Wain L, Cho M, Kaminski N, Zhao H. A statistical framework to identify cell types whose genetically regulated proportions are associated with complex diseases. PLOS Genetics 2023, 19: e1010825. PMID: 37523391, PMCID: PMC10414598, DOI: 10.1371/journal.pgen.1010825.Peer-Reviewed Original ResearchConceptsCell typesDisease-associated tissuesWide association studyComplex diseasesCell type proportionsDisease-relevant tissuesReal GWAS dataFunctional genesTranscriptomic dataGWAS dataGenetic dataAssociation studiesNovel statistical frameworkChronic obstructive pulmonary diseaseStatistical frameworkObstructive pulmonary diseaseIdiopathic pulmonary fibrosisBreast cancer riskType proportionsBlood CD8Pulmonary diseasePulmonary fibrosisPredictive biomarkersLung tissueBreast cancer