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 diseasesWDR5 Stabilizes Actin Architecture to Promote Multiciliated Cell Formation
Kulkarni SS, Griffin JN, Date PP, Liem KF, Khokha MK. WDR5 Stabilizes Actin Architecture to Promote Multiciliated Cell Formation. Developmental Cell 2018, 46: 595-610.e3. PMID: 30205038, PMCID: PMC6177229, DOI: 10.1016/j.devcel.2018.08.009.Peer-Reviewed Original ResearchConceptsMulticiliated cellsF-actinBasal bodiesHundreds of ciliaApical actin networkApical F-actinApical actinChromatin modificationsChromatin modifiersTissue morphogenesisActin cytoskeletonActin architectureActin networkWDR5Intracellular organellesG-actinCell surfaceCell formationCellsCytoskeletonMorphogenesisOrganellesRegulatorActinBindsCongenital 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 ciliaNup93GenomicsComplexesGenesKnockdownDuplicationPatterningMechanismThe heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality
Boskovski MT, Yuan S, Pedersen NB, Goth CK, Makova S, Clausen H, Brueckner M, Khokha MK. The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality. Nature 2013, 504: 456-459. PMID: 24226769, PMCID: PMC3869867, DOI: 10.1038/nature12723.Peer-Reviewed Original Research
2024
Unraveling the genetic tapestry of pediatric sarcomeric cardiomyopathies and masquerading phenocopies in Jordan
Azab B, Aburizeg D, Shaaban S, Ji W, Mustafa L, Isbeih N, Al-Akily A, Mohammad H, Jeffries L, Khokha M, Lakhani S, Al-Ammouri I. Unraveling the genetic tapestry of pediatric sarcomeric cardiomyopathies and masquerading phenocopies in Jordan. Scientific Reports 2024, 14: 15141. PMID: 38956129, PMCID: PMC11219879, DOI: 10.1038/s41598-024-64921-9.Peer-Reviewed Original ResearchConceptsExome sequencingSarcomere-related genesMitochondrial-related diseasesAt-risk family membersGenetic architectureGenetic landscapePathogenic variantsGene panelPediatric cardiomyopathyMolecular underpinningsGenetic testingPhenocopiesSarcomeric cardiomyopathiesGenesSequenceStorage disorderFamily membersAt-riskVariantsEarly interventionExomeFamilyGlycogen storage disorderHypertrophic cardiomyopathyCardiomyopathy
2023
SMC5 Plays Independent Roles in Congenital Heart Disease and Neurodevelopmental Disability
O'Brien M, Pryzhkova M, Lake E, Mandino F, Shen X, Karnik R, Atkins A, Xu M, Ji W, Konstantino M, Brueckner M, Ment L, Khokha M, Jordan P. SMC5 Plays Independent Roles in Congenital Heart Disease and Neurodevelopmental Disability. International Journal Of Molecular Sciences 2023, 25: 430. PMID: 38203602, PMCID: PMC10779392, DOI: 10.3390/ijms25010430.Peer-Reviewed Original Research
2017
White paper on the study of birth defects
Khokha MK, Mitchell LE, Wallingford JB. White paper on the study of birth defects. Birth Defects Research 2017, 109: 180-185. PMID: 28398650, DOI: 10.1002/bdra.23590.Peer-Reviewed Original Research