Featured Publications
RAPGEF5 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
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 ResearchMeSH KeywordsAnimalsBody PatterningCiliaHeart Defects, CongenitalHeterotaxy SyndromeMutation, MissensePhenotypeXenopusXenopus ProteinsConceptsLeft-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
2022
Mink1 regulates spemann organizer cell fate in the xenopus gastrula via Hmga2
Colleluori V, Khokha M. Mink1 regulates spemann organizer cell fate in the xenopus gastrula via Hmga2. Developmental Biology 2022, 495: 42-53. PMID: 36572140, PMCID: PMC10116378, DOI: 10.1016/j.ydbio.2022.11.010.Peer-Reviewed Original ResearchConceptsSpemann organizerCell fateTranscription factorsMolecular mechanismsSerine/threonine kinaseLeft-right patterningProper heart developmentUnbiased proteomic approachArchitectural transcription factorPlausible molecular mechanismCHD candidate genesVertebrate embryosThreonine kinaseProteomic approachXenopus gastrulaCommon birth defectsHeart developmentCandidate genesCanonical WntOrganizer cellsSequencing studiesMINK1Critical effectorΒ-cateninHMGA2
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