Featured Publications
Mechanical stretch scales centriole number to apical area via Piezo1 in multiciliated cells
Kulkarni S, Marquez J, Date P, Ventrella R, Mitchell B, Khokha M. Mechanical stretch scales centriole number to apical area via Piezo1 in multiciliated cells. ELife 2021, 10: e66076. PMID: 34184636, PMCID: PMC8270640, DOI: 10.7554/elife.66076.Peer-Reviewed Original ResearchConceptsCentriole numberMulticiliated cellsCentriole amplificationHundreds of centriolesOptimal cell functionTension-dependent mannerMechanosensitive ion channelsEmbryonic elongationOrganelle numberCell biologyNumber controlIon channelsCentriolesMost cellsPiezo1Multiple ciliaCell functionMCC functionMechanical forcesApical areaCiliaCellsPotential roleAmplificationFundamental questionsWDR5 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 formationCellsCytoskeletonMorphogenesisOrganellesRegulatorActinBindsRAPGEF5 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 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
Conserved chromatin and repetitive patterns reveal slow genome evolution in frogs
Bredeson J, Mudd A, Medina-Ruiz S, Mitros T, Smith O, Miller K, Lyons J, Batra S, Park J, Berkoff K, Plott C, Grimwood J, Schmutz J, Aguirre-Figueroa G, Khokha M, Lane M, Philipp I, Laslo M, Hanken J, Kerdivel G, Buisine N, Sachs L, Buchholz D, Kwon T, Smith-Parker H, Gridi-Papp M, Ryan M, Denton R, Malone J, Wallingford J, Straight A, Heald R, Hockemeyer D, Harland R, Rokhsar D. Conserved chromatin and repetitive patterns reveal slow genome evolution in frogs. Nature Communications 2024, 15: 579. PMID: 38233380, PMCID: PMC10794172, DOI: 10.1038/s41467-023-43012-9.Peer-Reviewed Original ResearchConceptsCENP-A bindingChromosome-scale sequencesRabl-like configurationConservation of syntenyChromatin conformation captureMeiotic linkage mapWestern clawed frogEnd-to-end fusionsStructure of chromosomesDevelopmental model systemRate of recombinationAnuran chromosomesConformation captureFrog genomeGenome evolutionCentromeric chromatinGenus XenopusFrog speciesLinkage mapPhylogenetically ancient groupCentromere locationSmall chromosomesX. tropicalisSatellite repeatsEngystomops pustulosus
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 ResearchCFAP45, a heterotaxy and congenital heart disease gene, affects cilia stability
Deniz E, Pasha M, Guerra M, Viviano S, Ji W, Konstantino M, Jeffries L, Lakhani S, Medne L, Skraban C, Krantz I, Khokha M. CFAP45, a heterotaxy and congenital heart disease gene, affects cilia stability. Developmental Biology 2023, 499: 75-88. PMID: 37172641, PMCID: PMC10373286, DOI: 10.1016/j.ydbio.2023.04.006.Peer-Reviewed Original ResearchConceptsLeft-right organizerCilia stabilityLeft-right patterningCongenital heart disease genesApical surfaceCell apical surfaceLive confocal imagingLeftward fluid flowHeart disease genesRecessive missense mutationLethal birth defectMotile monociliaProtein familyEarly embryogenesisMulticiliated cellsCiliary axonemeDisease genesFrog embryosGenetic underpinningsWhole-exome sequencingMissense mutationsConfocal imagingEmbryosCiliaCongenital heart disease
2020
Disrupted ER membrane protein complex-mediated topogenesis drives congenital neural crest defects
Marquez J, Criscione J, Charney RM, Prasad MS, Hwang WY, Mis EK, García-Castro MI, Khokha MK. Disrupted ER membrane protein complex-mediated topogenesis drives congenital neural crest defects. Journal Of Clinical Investigation 2020, 130: 813-826. PMID: 31904590, PMCID: PMC6994125, DOI: 10.1172/jci129308.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulum (ER) membrane protein complexMultipass membrane proteinsNeural crest cellsMembrane proteinsHuman NCC developmentER membrane proteinsMembrane protein complexesCell-cell signalsMyriad of functionsNCC defectsNCC developmentProtein complexesUnbiased proteomicsXenopus modelTransmembrane proteinFunction allelesPatient phenotypesCrest cellsMolecular connectionNeural crestMolecular mechanismsBirth defectsPatient variantsEMC1Β-catenin
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