2020
An allosteric site on MKP5 reveals a strategy for small-molecule inhibition
Gannam Z, Min K, Shillingford SR, Zhang L, Herrington J, Abriola L, Gareiss PC, Pantouris G, Tzouvelekis A, Kaminski N, Zhang X, Yu J, Jamali H, Ellman JA, Lolis E, Anderson KS, Bennett AM. An allosteric site on MKP5 reveals a strategy for small-molecule inhibition. Science Signaling 2020, 13 PMID: 32843541, PMCID: PMC7569488, DOI: 10.1126/scisignal.aba3043.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric SiteAmino Acid SequenceAnimalsCell DifferentiationCell LineDual-Specificity PhosphatasesEnzyme InhibitorsFemaleHigh-Throughput Screening AssaysHumansKineticsMiceMice, KnockoutMitogen-Activated Protein Kinase PhosphatasesMyoblastsProtein BindingSequence Homology, Amino AcidSignal TransductionSmall Molecule LibrariesConceptsDystrophic muscle diseaseMitogen-activated protein kinaseMuscle diseaseTGF-β1Promising therapeutic targetP38 mitogen-activated protein kinaseTherapeutic strategiesTherapeutic targetSmall molecule inhibitionSmad2 phosphorylationDiseasePotential targetSmall-molecule screenInhibitorsTreatmentInhibition
2018
iDREM: 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
2014
Nrf2 Amplifies Oxidative Stress via Induction of Klf9
Zucker SN, Fink EE, Bagati A, Mannava S, Bianchi-Smiraglia A, Bogner PN, Wawrzyniak JA, Foley C, Leonova KI, Grimm MJ, Moparthy K, Ionov Y, Wang J, Liu S, Sexton S, Kandel ES, Bakin AV, Zhang Y, Kaminski N, Segal BH, Nikiforov MA. Nrf2 Amplifies Oxidative Stress via Induction of Klf9. Molecular Cell 2014, 53: 916-928. PMID: 24613345, PMCID: PMC4049522, DOI: 10.1016/j.molcel.2014.01.033.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesBleomycinCell Line, TumorGene Expression RegulationGenes, ReporterHumansKruppel-Like Transcription FactorsLuciferasesLungMiceNF-E2-Related Factor 2NIH 3T3 CellsOxidative StressPromoter Regions, GeneticProtein BindingPulmonary FibrosisReactive Oxygen SpeciesSignal TransductionConceptsReactive oxygen speciesKey transcriptional regulatorMetabolism of ROSOxidative stressPathogenesis of bleomycinKruppel-like factor 9Thioredoxin reductase 2Subsequent cell deathTranscription factor 2Antioxidant gene expressionUbiquitous regulatorsTranscriptional regulatorsIntracellular reactive oxygen speciesLung injuryFeedforward regulationPulmonary fibrosisGene expressionOxidant injuryROS clearanceCell deathReductase 2Mouse tissuesCultured cellsNF-E2Factor 9
2011
High Throughput Determination of TGFβ1/SMAD3 Targets in A549 Lung Epithelial Cells
Zhang Y, Handley D, Kaplan T, Yu H, Bais AS, Richards T, Pandit KV, Zeng Q, Benos PV, Friedman N, Eickelberg O, Kaminski N. High Throughput Determination of TGFβ1/SMAD3 Targets in A549 Lung Epithelial Cells. PLOS ONE 2011, 6: e20319. PMID: 21625455, PMCID: PMC3098871, DOI: 10.1371/journal.pone.0020319.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceCell LineChromatin ImmunoprecipitationDNA PrimersElectrophoretic Mobility Shift AssayEpithelial CellsHumansLungOligonucleotide Array Sequence AnalysisPromoter Regions, GeneticProtein BindingReverse Transcriptase Polymerase Chain ReactionSmad3 ProteinTransforming Growth Factor beta1ConceptsGene expression microarraysLung epithelial cellsMolecular pathwaysTranscriptional regulationExpression microarraysGlobal transcriptional regulationTGFβ1/Smad3Epithelial cellsHuman promoter regionsSignal transduction cascadeTarget gene expressionEpithelial cell phenotypeGene expression analysisTranscription factor Smad3Primary lung epithelial cellsSmad3 targetsQuantitative real-time RT-PCRFOXA2 promoterHuman A549 alveolar epithelial cellsChromatin immunoprecipitationTransduction cascadeTarget genesA549 lung epithelial cellsExpression analysisGene expression
2008
Cross Talk between Id1 and Its Interactive Protein Dril1 Mediate Fibroblast Responses to Transforming Growth Factor-β in Pulmonary Fibrosis
Lin L, Zhou Z, Zheng L, Alber S, Watkins S, Ray P, Kaminski N, Zhang Y, Morse D. Cross Talk between Id1 and Its Interactive Protein Dril1 Mediate Fibroblast Responses to Transforming Growth Factor-β in Pulmonary Fibrosis. American Journal Of Pathology 2008, 173: 337-346. PMID: 18583319, PMCID: PMC2475772, DOI: 10.2353/ajpath.2008.070915.Peer-Reviewed Original ResearchConceptsLung fibrosisPulmonary fibrosisGrowth factorSuppression of fibrosisTranscriptional regulator inhibitorIdiopathic pulmonary fibrosisProgressive lung fibrosisEffects of Id1Activation of TGFInhibited DNA bindingProfibrotic functionsDisease progressionFibrosisFibrotic diseasesDifferentiation 1TGFPotential mechanismsId1FibroblastsNovel binding partnerHuman fibroblastsDRIL1Target genesPatientsLung
1999
A Mechanism for Regulating Pulmonary Inflammation and Fibrosis: The Integrin αvβ6 Binds and Activates Latent TGF β1
Munger J, Huang X, Kawakatsu H, Griffiths M, Dalton S, Wu J, Pittet J, Kaminski N, Garat C, Matthay M, Rifkin D, Sheppard D. A Mechanism for Regulating Pulmonary Inflammation and Fibrosis: The Integrin αvβ6 Binds and Activates Latent TGF β1. Cell 1999, 96: 319-328. PMID: 10025398, DOI: 10.1016/s0092-8674(00)80545-0.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAnimalsAntigens, NeoplasmBleomycinCHO CellsCricetinaeEpithelial CellsEsophagusHumansIntegrinsKeratinocytesLigandsMiceMice, KnockoutPeptide FragmentsProtein BindingProtein PrecursorsProteinsPulmonary FibrosisTransforming Growth Factor betaTransforming Growth Factor beta1Tumor Cells, CulturedConceptsLatency-associated peptideIntegrin alpha v beta 6Alpha v beta 6 integrinAlpha v beta 6Beta gene productsTGF beta 1Latent TGF-β1TGF-beta functionGrowth factor-beta (TGF-beta) family membersPulmonary inflammationExaggerated inflammationPulmonary fibrosisTGF-β1Beta 6Alpha vBeta 1Beta family membersInflammationFibrosisFamily membersNovel mechanismExtracellular activationVivoActivationIntegrins