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 programmicroRNA-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
2023
Integrative 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 ResearchMeSH KeywordsGenomicsHumansLungLung Diseases, InterstitialMicroRNAsPulmonary Disease, Chronic ObstructiveConceptsSeed sequenceGene expressionShort RNA sequencingAirway differentiationIntegrative network analysisExpression networksRNA sequencingGenomic networksMiRNA regulatorsMiRNA isoformsNotch pathwayIsomiRsDistinct subclustersSNP microarraysGenesMicroRNAsMolecular heterogeneityILD pathogenesisDisease networkOverexpressionSequenceExpressionNetwork analysisDifferentiationGrb2
2021
MicroRNA miR-24-3p reduces DNA damage responses, apoptosis, and susceptibility to chronic obstructive pulmonary disease
Nouws J, Wan F, Finnemore E, Roque W, Kim SJ, Bazan IS, Li CX, Sköld C, Dai Q, Yan X, Chioccioli M, Neumeister V, Britto CJ, Sweasy J, Bindra RS, Wheelock ÅM, Gomez JL, Kaminski N, Lee PJ, Sauler M. MicroRNA miR-24-3p reduces DNA damage responses, apoptosis, and susceptibility to chronic obstructive pulmonary disease. JCI Insight 2021, 6: e134218. PMID: 33290275, PMCID: PMC7934877, DOI: 10.1172/jci.insight.134218.Peer-Reviewed Original ResearchConceptsCellular stress responseStress responseHomology-directed DNA repairDNA damage responseProtein BRCA1Damage responseCellular stressDNA repairProtein BimCOPD lung tissueLung epithelial cellsCellular responsesExpression arraysEpithelial cell apoptosisDNA damageChronic obstructive pulmonary diseaseBRCA1 expressionCell apoptosisApoptosisEpithelial cellsCritical mechanismMicroRNAsRegulatorObstructive pulmonary diseaseIncreases Susceptibility
2020
Retrograde signaling by a mtDNA-encoded non-coding RNA preserves mitochondrial bioenergetics
Blumental-Perry A, Jobava R, Bederman I, Degar A, Kenche H, Guan B, Pandit K, Perry N, Molyneaux N, Wu J, Prendergas E, Ye Z, Zhang J, Nelson C, Ahangari F, Krokowski D, Guttentag S, Linden P, Townsend D, Miron A, Kang M, Kaminski N, Perry Y, Hatzoglou M. Retrograde signaling by a mtDNA-encoded non-coding RNA preserves mitochondrial bioenergetics. Communications Biology 2020, 3: 626. PMID: 33127975, PMCID: PMC7603330, DOI: 10.1038/s42003-020-01322-4.Peer-Reviewed Original ResearchConceptsMitochondrial genomeNuclear-encoded genesCell type-specific mannerNon-coding RNASteady-state transcriptionMitochondrial energy metabolismControl regionPositive regulationMitochondrial bioenergeticsMitochondria stressMitochondrial functionSpecific mannerAlveolar epithelial type II cellsEnergy metabolismType II cellsEpithelial type II cellsGenomePhysiological stressRNAII cellsCellsMouse lungTranscriptionGenesMitochondria
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
2018
Hypercapnia increases airway smooth muscle contractility via caspase-7–mediated miR-133a–RhoA signaling
Shigemura M, Lecuona E, Angulo M, Homma T, Rodríguez DA, Gonzalez-Gonzalez FJ, Welch LC, Amarelle L, Kim SJ, Kaminski N, Budinger GRS, Solway J, Sznajder JI. Hypercapnia increases airway smooth muscle contractility via caspase-7–mediated miR-133a–RhoA signaling. Science Translational Medicine 2018, 10 PMID: 30185650, PMCID: PMC6889079, DOI: 10.1126/scitranslmed.aat1662.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAgedAged, 80 and overAirway ResistanceAnimalsCalciumCalpainCarbon DioxideCaspase 7Chronic DiseaseDown-RegulationEnzyme ActivationFemaleHumansHypercapniaMaleMEF2 Transcription FactorsMice, Inbred C57BLMicroRNAsMiddle AgedMuscle ContractionMuscle, SmoothMyocytes, Smooth MusclePulmonary Disease, Chronic ObstructiveRhoA GTP-Binding ProteinSignal TransductionConceptsChronic obstructive pulmonary diseaseAirway smooth muscle cellsSmooth muscle cellsMouse airway smooth muscle cellsSevere chronic obstructive pulmonary diseaseHuman airway smooth muscle cellsAirway smooth muscle contractilityMuscle cellsCorrection of hypercapniaSmooth muscle cell contractionCohort of patientsObstructive pulmonary diseaseHigh airway resistanceSevere lung diseaseDevelopment of hypercapniaSmooth muscle contractilityMuscle cell contractionRas homolog family member AMyosin light chain phosphorylationAirway contractilityAirway contractionHypercapnic patientsCOPD severityPulmonary diseaseAirway resistanceiDREM: Interactive visualization of dynamic regulatory networks
Ding J, Hagood JS, Ambalavanan N, Kaminski N, Bar-Joseph Z. iDREM: Interactive visualization of dynamic regulatory networks. PLOS Computational Biology 2018, 14: e1006019. PMID: 29538379, PMCID: PMC5868853, DOI: 10.1371/journal.pcbi.1006019.Peer-Reviewed Original ResearchConceptsDynamic regulatory networksRegulatory networksHigh-throughput time series dataInteraction dataProtein-DNA interaction dataSingle-cell RNA-seqTime series gene expression dataStatic datasetsInteractive visualizationGene expression dataData typesRNA-seqTime series dataBiological processesExpression dataMiRNA expressionNetworkSeries dataImportant challengeNew versionDevelopmental dataNovel hypothesisUnified modelMultiple labsRecent years
2017
Lung Endothelial MicroRNA-1 Regulates Tumor Growth and Angiogenesis
Korde A, Jin L, Zhang JG, Ramaswamy A, Hu B, Kolahian S, Guardela BJ, Herazo-Maya J, Siegfried JM, Stabile L, Pisani MA, Herbst RS, Kaminski N, Elias JA, Puchalski JT, Takyar SS. Lung Endothelial MicroRNA-1 Regulates Tumor Growth and Angiogenesis. American Journal Of Respiratory And Critical Care Medicine 2017, 196: 1443-1455. PMID: 28853613, PMCID: PMC5736970, DOI: 10.1164/rccm.201610-2157oc.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerMiR-1 levelsLewis lung carcinoma xenograftsLung carcinoma xenograftsTransgenic miceEndothelial cellsNSCLC tumorsCarcinoma xenograftsLung endotheliumMiR-1Tumor growthTumor progressionVascular endothelial cadherin promoterMicroRNA-1Cohort of patientsTumor-bearing lungsCell lung cancerVascular endothelial growth factorCancer-free tissuesEndothelial growth factorInducible transgenic miceMiR-1 overexpressionKP miceOverall survivalTumor burdenModified mesenchymal stem cells using miRNA transduction alter lung injury in a bleomycin model
Huleihel L, Sellares J, Cardenes N, Álvarez D, Faner R, Sakamoto K, Yu G, Kapetanaki MG, Kaminski N, Rojas M. Modified mesenchymal stem cells using miRNA transduction alter lung injury in a bleomycin model. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2017, 313: l92-l103. PMID: 28385811, PMCID: PMC5538868, DOI: 10.1152/ajplung.00323.2016.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersBleomycinBone Marrow CellsCollagenCytokinesDisease Models, AnimalFemaleGene Expression RegulationGene Regulatory NetworksHumansInterleukin-6Leukocyte Common AntigensLung InjuryMesenchymal Stem Cell TransplantationMesenchymal Stem CellsMice, Inbred C57BLMicroRNAsRNA, MessengerSurvival AnalysisTransduction, GeneticTransfectionWeight LossConceptsBone marrow-derived mesenchymal stem cellsMesenchymal stem cellsLung fibrosisLate administrationBleomycin modelMiR-154Different preclinical modelsStem cellsCD45-positive cellsMurine bleomycin modelMarrow-derived mesenchymal stem cellsInitial weight lossLower survival rateAshcroft scoreLung injuryBleomycin instillationFibrotic changesCytokine expressionMice groupsLung tissueOH-prolinePreclinical modelsProtective effectTreatment groupsSurvival rate
2015
Regulation of alveolar septation by microRNA-489
Olave N, Lal CV, Halloran B, Pandit K, Cuna AC, Faye-Petersen OM, Kelly DR, Nicola T, Benos PV, Kaminski N, Ambalavanan N. Regulation of alveolar septation by microRNA-489. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2015, 310: l476-l487. PMID: 26719145, PMCID: PMC4773841, DOI: 10.1152/ajplung.00145.2015.Peer-Reviewed Original ResearchConceptsBronchopulmonary dysplasiaMiR-489Alveolar septationLung developmentInsulin-like growth factor-1Abnormal lung developmentGrowth factor-1MiR-489 overexpressionNormal pretermTerm infantsC57BL/6 miceMouse lung developmentTherapeutic strategiesMiRNA-489HyperoxiaEpithelial originFurther inhibitionIGF1Factor 1MiRNA antagonistsNormoxiaTenascin CMiRNA profilesCytomegalovirus promoterInfantsMesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs
Phinney DG, Di Giuseppe M, Njah J, Sala E, Shiva S, St Croix CM, Stolz DB, Watkins SC, Di YP, Leikauf GD, Kolls J, Riches DW, Deiuliis G, Kaminski N, Boregowda SV, McKenna DH, Ortiz LA. Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs. Nature Communications 2015, 6: 8472. PMID: 26442449, PMCID: PMC4598952, DOI: 10.1038/ncomms9472.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArrestinsBlotting, WesternCell-Derived MicroparticlesExosomesExtracellular VesiclesFlow CytometryHumansMacrophagesMesenchymal Stem CellsMiceMicroRNAsMicroscopy, ElectronMitochondriaMitophagyMyeloid Differentiation Factor 88Oxidative StressReceptors, ImmunologicSignal TransductionSilicosisToll-Like Receptor 4Toll-Like Receptor 9Toll-Like ReceptorsConceptsMesenchymal stem cellsStem cellsDomain-containing protein 1Stem cell nicheHealthy mitochondrial functionHaematopoietic stem cellsCell nichePlasma membraneToll-like receptor signalingIntracellular oxidative stressMitochondrial functionExtracellular vesiclesMicro RNAsReceptor signalingProtein 1MitophagyMSC survivalMitochondriaOxidative stressMacrophage functionVesiclesCellsRecent studiesMacrophage activationMacrophages
2014
Assessment of microRNA differential expression and detection in multiplexed small RNA sequencing data
Campbell JD, Liu G, Luo L, Xiao J, Gerrein J, Juan-Guardela B, Tedrow J, Alekseyev YO, Yang IV, Correll M, Geraci M, Quackenbush J, Sciurba F, Schwartz DA, Kaminski N, Johnson WE, Monti S, Spira A, Beane J, Lenburg ME. Assessment of microRNA differential expression and detection in multiplexed small RNA sequencing data. RNA 2014, 21: 164-171. PMID: 25519487, PMCID: PMC4338344, DOI: 10.1261/rna.046060.114.Peer-Reviewed Original ResearchMatrix Metalloproteinase-19 Promotes Metastatic Behavior In Vitro and Is Associated with Increased Mortality in Non–Small Cell Lung Cancer
Yu G, Herazo-Maya JD, Nukui T, Romkes M, Parwani A, Juan-Guardela BM, Robertson J, Gauldie J, Siegfried JM, Kaminski N, Kass DJ. Matrix Metalloproteinase-19 Promotes Metastatic Behavior In Vitro and Is Associated with Increased Mortality in Non–Small Cell Lung Cancer. American Journal Of Respiratory And Critical Care Medicine 2014, 190: 780-790. PMID: 25250855, PMCID: PMC4299607, DOI: 10.1164/rccm.201310-1903oc.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerLung cancerEpithelial-mesenchymal transitionLung tumorsMatrix metalloproteinasesProgression of NSCLCNormal lung tissuesHuman lung cancerNSCLC cell linesMultiple NSCLC cell linesLung cancer tumorsMMP19 expressionPoor prognosisCancer deathControl subjectsIncreased MortalityLung tissueNSCLC cellsMolecular pathogenesisPotential biomarkersDisease severityMetastatic behaviorCancerCancer tumorsMicroRNA mimicry blocks pulmonary fibrosis
Montgomery RL, Yu G, Latimer PA, Stack C, Robinson K, Dalby CM, Kaminski N, van Rooij E. MicroRNA mimicry blocks pulmonary fibrosis. EMBO Molecular Medicine 2014, 6: 1347-1356. PMID: 25239947, PMCID: PMC4287936, DOI: 10.15252/emmm.201303604.Peer-Reviewed Original ResearchLet-7d microRNA affects mesenchymal phenotypic properties of lung fibroblasts
Huleihel L, Ben-Yehudah A, Milosevic J, Yu G, Pandit K, Sakamoto K, Yousef H, LeJeune M, Coon TA, Redinger CJ, Chensny L, Manor E, Schatten G, Kaminski N. Let-7d microRNA affects mesenchymal phenotypic properties of lung fibroblasts. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2014, 306: l534-l542. PMID: 24441869, PMCID: PMC3949080, DOI: 10.1152/ajplung.00149.2013.Peer-Reviewed Original ResearchMeSH KeywordsActinsCadherinsCalcium-Binding ProteinsCell MovementCell ProliferationCells, CulturedEpithelial-Mesenchymal TransitionFibroblastsFibronectinsHMGA2 ProteinHMGB2 ProteinHumansIdiopathic Pulmonary FibrosisKeratin-19LungMicroRNAsMyofibroblastsPulmonary AlveoliPulmonary FibrosisS100 Calcium-Binding Protein A4Snail Family Transcription FactorsTranscription FactorsTransfectionTransforming Growth Factor betaWound HealingZonula Occludens-1 ProteinConceptsLet-7dFibroblast-specific protein-1Mesenchymal marker αProtein 1Tight junction protein 1Smooth muscle actinMicroRNA Let-7dLung fibrosisProliferation of fibroblastsFibrotic processPrimary fibroblastsEffect of transfectionMuscle actinMesenchymal transitionLung fibroblastsFibroblast responsivenessMesenchymal propertiesKeratin 19Protein expressionEpithelial cellsWound healingN-cadherinProtein inductionReduced motilityTGF
2013
Reconstructing dynamic microRNA-regulated interaction networks
Schulz MH, Pandit KV, Cardenas C, Ambalavanan N, Kaminski N, Bar-Joseph Z. Reconstructing dynamic microRNA-regulated interaction networks. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 15686-15691. PMID: 23986498, PMCID: PMC3785769, DOI: 10.1073/pnas.1303236110.Peer-Reviewed Original ResearchConceptsTranscription factorsGene expressionDynamic Regulatory Events MinerTemporal gene expressionDynamic regulatory networksSpecific developmental phasesMRNA expression dataLung developmentRegulatory networksMiRNA targetsInteraction networksImportant miRNAsExpression dataMiRNAsAdditional miRNAsLung differentiationDevelopmental phasesMiRNAPostnatal lung developmentProgression pathwaysProliferation assaysExpressionRegulationMRNA expressionMicroRNAsExpression of Regulatory Platelet MicroRNAs in Patients with Sickle Cell Disease
Jain S, Kapetanaki MG, Raghavachari N, Woodhouse K, Yu G, Barge S, Coronnello C, Benos PV, Kato GJ, Kaminski N, Gladwin MT. Expression of Regulatory Platelet MicroRNAs in Patients with Sickle Cell Disease. PLOS ONE 2013, 8: e60932. PMID: 23593351, PMCID: PMC3625199, DOI: 10.1371/journal.pone.0060932.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnemia, Sickle CellBlood PlateletsCell LineChromosomes, Human, Pair 14Computational BiologyDown-RegulationFemaleGene Expression ProfilingGene Expression RegulationGenomic ImprintingHumansHydroxyureaMaleMegakaryocytesMicroRNAsMiddle AgedMolecular Sequence AnnotationOligonucleotide Array Sequence AnalysisReproducibility of ResultsTricuspid Valve InsufficiencyUp-RegulationYoung AdultConceptsMiRNA expression profilesExpression profilesMRNA targetsSignificant transcriptional repressionPlatelet miRNAsPost-transcriptional regulationMiRNA target sequencesComputational prediction analysisAltered miRNA expression profilesMRNA expression profilesExpression of miRNAsAgilent miRNA microarrayTranscriptional repressionPlatelet transcriptomeBiological pathwaysDownregulated miRNAsMiRNAsPlatelet transcriptsMiRNA microarrayPlatelet microRNAsTarget sequenceMiR-376aMiR-376QRT-PCRMiR-154miR-199a-5p Is Upregulated during Fibrogenic Response to Tissue Injury and Mediates TGFbeta-Induced Lung Fibroblast Activation by Targeting Caveolin-1
Cardenas C, Henaoui IS, Courcot E, Roderburg C, Cauffiez C, Aubert S, Copin MC, Wallaert B, Glowacki F, Dewaeles E, Milosevic J, Maurizio J, Tedrow J, Marcet B, Lo-Guidice JM, Kaminski N, Barbry P, Luedde T, Perrais M, Mari B, Pottier N. miR-199a-5p Is Upregulated during Fibrogenic Response to Tissue Injury and Mediates TGFbeta-Induced Lung Fibroblast Activation by Targeting Caveolin-1. PLOS Genetics 2013, 9: e1003291. PMID: 23459460, PMCID: PMC3573122, DOI: 10.1371/journal.pgen.1003291.Peer-Reviewed Original ResearchConceptsIdiopathic formMiR-199aIPF patientsMouse modelUnilateral ureteral obstruction (UUO) mouse modelLung fibroblastsFibrotic lung diseaseLung fibroblast activationBile duct ligationPoor response ratesNew therapeutic strategiesCultured lung fibroblastsDifferent mouse strainsKey cell typesPulmonary expressionHistologic featuresPulmonary fibrosisFibroblastic fociLung diseaseLung fibrosisCurrent therapiesFibrogenic responseKidney fibrosisLiver fibrosisBleomycin exposure