Featured Publications
Membrane potential drives the exit from pluripotency and cell fate commitment via calcium and mTOR
Sempou E, Kostiuk V, Zhu J, Cecilia Guerra M, Tyan L, Hwang W, Camacho-Aguilar E, Caplan M, Zenisek D, Warmflash A, Owens N, Khokha M. Membrane potential drives the exit from pluripotency and cell fate commitment via calcium and mTOR. Nature Communications 2022, 13: 6681. PMID: 36335122, PMCID: PMC9637099, DOI: 10.1038/s41467-022-34363-w.Peer-Reviewed Original ResearchConceptsPluripotent cellsAdult tissue homeostasisCell fate commitmentDifferentiated cell fatesLeft-right patterningPluripotent embryonic cellsHuman embryonic stem cellsTemporal transcriptome analysisGene regulatory networksExpense of differentiationEmbryonic stem cellsGerm layer differentiationMembrane depolarizationFate commitmentPluripotent stateCell fateTranscriptome analysisRegulatory networksMyogenic lineageEmbryonic developmentTissue homeostasisDifferentiated fateEmbryonic cellsCandidate genesPluripotencyKap-β2/Transportin mediates β-catenin nuclear transport in Wnt signaling
Hwang WY, Kostiuk V, González DP, Lusk CP, Khokha M. Kap-β2/Transportin mediates β-catenin nuclear transport in Wnt signaling. ELife 2022, 11: e70495. PMID: 36300792, PMCID: PMC9665845, DOI: 10.7554/elife.70495.Peer-Reviewed Original ResearchConceptsNuclear transport receptorsΒ-catenin nuclear transportNuclear transportΒ-cateninExcessive WntΒ-catenin nuclear importHeterologous model systemsΒ-catenin accumulatesPrimary embryonic axisNuclear transport machineryRan-dependent mannerNuclear localization signalTCF/LEF reporterPY-NLSNuclear importLocalization signalTransport machineryTransport receptorsResponsive genesEmbryonic developmentEmbryonic axisWnt signalingKey effectorsDirect bindingHuman diseasesRAPGEF5 Regulates Nuclear Translocation of β-Catenin
Griffin JN, del Viso F, Duncan AR, Robson A, Hwang W, Kulkarni S, Liu KJ, Khokha MK. RAPGEF5 Regulates Nuclear Translocation of β-Catenin. Developmental Cell 2017, 44: 248-260.e4. PMID: 29290587, PMCID: PMC5818985, DOI: 10.1016/j.devcel.2017.12.001.Peer-Reviewed Original ResearchConceptsLeft-right patterningNuclear transportΒ-cateninNuclear transport pathwaysΒ-catenin nuclear transportNuclear translocationRap1a/bExchange factorCytoplasmic stabilizationEmbryonic developmentNuclear localizationCanonical WntRAPGEF5WntPathway activationNew targetsTransport pathwaysTranslocationPatterningDisease statesTransport systemGTPasesIntensive investigationGuanineCommon diseaseCongenital Heart Disease Genetics Uncovers Context-Dependent Organization and Function of Nucleoporins at Cilia
del Viso F, Huang F, Myers J, Chalfant M, Zhang Y, Reza N, Bewersdorf J, Lusk CP, Khokha MK. Congenital Heart Disease Genetics Uncovers Context-Dependent Organization and Function of Nucleoporins at Cilia. Developmental Cell 2016, 38: 478-492. PMID: 27593162, PMCID: PMC5021619, DOI: 10.1016/j.devcel.2016.08.002.Peer-Reviewed Original ResearchConceptsNuclear pore complexPore complexCiliary pore complexLeft-right patterningBarrel-like structureNPC functionEmbryonic developmentCandidate genesNup188Human genomicsNanoscale organizationNucleoporinsDirect roleSuper-resolution imagingCiliaLoss of ciliaNup93GenomicsComplexesGenesKnockdownDuplicationPatterningMechanism
2016
Measuring Absolute RNA Copy Numbers at High Temporal Resolution Reveals Transcriptome Kinetics in Development
Owens NDL, Blitz IL, Lane MA, Patrushev I, Overton JD, Gilchrist MJ, Cho KWY, Khokha MK. Measuring Absolute RNA Copy Numbers at High Temporal Resolution Reveals Transcriptome Kinetics in Development. Cell Reports 2016, 14: 632-647. PMID: 26774488, PMCID: PMC4731879, DOI: 10.1016/j.celrep.2015.12.050.Peer-Reviewed Original ResearchConceptsQuantitative biologyCell fate decisionsGene expression trajectoriesCommon gene functionsEmbryonic transcriptsFate decisionsGene functionTranscript regulationAbsolute transcript numbersExpression dynamicsTranscriptome kineticsEmbryonic developmentXenopus embryosExpression trajectoriesCellular metabolismGene expressionTranscript numbersUnprecedented insightsCell functionGenesBiologySynexpressionMisregulationTranscriptomeDevelopmental period