Featured Publications
Mutations in KATNB1 Cause Complex Cerebral Malformations by Disrupting Asymmetrically Dividing Neural Progenitors
Mishra-Gorur K, Çağlayan AO, Schaffer AE, Chabu C, Henegariu O, Vonhoff F, Akgümüş GT, Nishimura S, Han W, Tu S, Baran B, Gümüş H, Dilber C, Zaki MS, Hossni HA, Rivière JB, Kayserili H, Spencer EG, Rosti RÖ, Schroth J, Per H, Çağlar C, Çağlar Ç, Dölen D, Baranoski JF, Kumandaş S, Minja FJ, Erson-Omay EZ, Mane SM, Lifton RP, Xu T, Keshishian H, Dobyns WB, C. N, Šestan N, Louvi A, Bilgüvar K, Yasuno K, Gleeson JG, Günel M. Mutations in KATNB1 Cause Complex Cerebral Malformations by Disrupting Asymmetrically Dividing Neural Progenitors. Neuron 2014, 84: 1226-1239. PMID: 25521378, PMCID: PMC5024344, DOI: 10.1016/j.neuron.2014.12.014.Peer-Reviewed Original ResearchConceptsComplex cerebral malformationsCerebral cortical malformationsMicrotubule-severing enzyme kataninExome sequencing analysisMitotic spindle formationDrosophila optic lobeCerebral malformationsPatient-derived fibroblastsCell cycle progression delayCortical malformationsMotor neuronsComplex malformationsMicrotubule-associated proteinsCortical developmentReduced cell numberOptic lobeRegulatory subunitBrain developmentCatalytic subunitDeleterious mutationsSpindle formationSupernumerary centrosomesArborization defectsMalformationsHuman phenotypes
2013
Mutations in CSPP1 Lead to Classical Joubert Syndrome
Akizu N, Silhavy JL, Rosti RO, Scott E, Fenstermaker AG, Schroth J, Zaki MS, Sanchez H, Gupta N, Kabra M, Kara M, Ben-Omran T, Rosti B, Guemez-Gamboa A, Spencer E, Pan R, Cai N, Abdellateef M, Gabriel S, Halbritter J, Hildebrandt F, van Bokhoven H, Gunel M, Gleeson JG. Mutations in CSPP1 Lead to Classical Joubert Syndrome. American Journal Of Human Genetics 2013, 94: 80-86. PMID: 24360807, PMCID: PMC3882909, DOI: 10.1016/j.ajhg.2013.11.015.Peer-Reviewed Original ResearchConceptsJoubert syndromeDistinctive mid-hindbrain malformationMid-hindbrain malformationPrimary cilia dysfunctionPrimary ciliaKidney diseaseLarge cohortVariable involvementRelated disordersHuman neurogenesisNeural tissueProtein levelsAffected individualsSyndromeCilia dysfunctionCohortNeural-specific functionsCausative mutationsMutationsNull mutationCSPP1IndividualsCiliaDysfunctionJSRD
2011
The Essential Role of Centrosomal NDE1 in Human Cerebral Cortex Neurogenesis
Bakircioglu M, Carvalho OP, Khurshid M, Cox JJ, Tuysuz B, Barak T, Yilmaz S, Caglayan O, Dincer A, Nicholas AK, Quarrell O, Springell K, Karbani G, Malik S, Gannon C, Sheridan E, Crosier M, Lisgo SN, Lindsay S, Bilguvar K, Gergely F, Gunel M, Woods CG. The Essential Role of Centrosomal NDE1 in Human Cerebral Cortex Neurogenesis. American Journal Of Human Genetics 2011, 88: 523-535. PMID: 21529752, PMCID: PMC3146716, DOI: 10.1016/j.ajhg.2011.03.019.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Cycle ProteinsCentrosomeCerebral CortexChild, PreschoolDNA Mutational AnalysisEpithelial CellsExonsFemaleGenetic LinkageHeLa CellsHomozygoteHumansInfantMaleMiceMicrocephalyMicrotubule-Associated ProteinsMutationNeural Stem CellsNeurogenesisNeuronsPhenotypePregnancyRNA, MessengerTransfectionConceptsCortical laminationPatient-derived cell linesDistinct homozygous mutationsProfound mental retardationCerebral cortexCerebral cortex neurogenesisMouse embryonic brainNeuron productionBrain scansPostmortem dataEmbryonic brainNeural precursorsHomozygous mutationNeuroepithelial cellsNeurogenesisPatient cellsMental retardationExtreme microcephalyAffected individualsEarly neurogenesisCell linesT mutationPakistani originBrainTurkish family
2005
CCM2 Expression Parallels That of CCM1
Seker A, Pricola KL, Guclu B, Ozturk AK, Louvi A, Gunel M. CCM2 Expression Parallels That of CCM1. Stroke 2005, 37: 518-523. PMID: 16373645, DOI: 10.1161/01.str.0000198835.49387.25.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternBrainCarrier ProteinsCells, CulturedCentral Nervous SystemCerebral CortexChlorocebus aethiopsCOS CellsEndothelium, VascularHumansImmunohistochemistryIn Situ HybridizationKRIT1 ProteinMiceMicrotubule-Associated ProteinsMuscle, SmoothMutationNeuronsPhenotypeProto-Oncogene ProteinsRNA, MessengerSignal TransductionTime FactorsTwo-Hybrid System TechniquesUmbilical VeinsConceptsCerebral cavernous malformationsProtein expressionExtracerebral tissuesFamilial cerebral cavernous malformationsArterial vascular endotheliumPostnatal mouse brainSmooth muscle cellsVascular wall elementsWestern blot analysisExpression patternsPyramidal neuronsVenous circulationCerebral tissueNeurovascular diseasesCavernous malformationsImmunohistochemical analysisVascular endotheliumMouse brainMRNA expressionMuscle cellsFoot processesEpithelial cellsExpression parallelsDisease phenotypeSpatial expression patternsCerebral Venous Malformations Have Distinct Genetic Origin From Cerebral Cavernous Malformations
Guclu B, Ozturk AK, Pricola KL, Seker A, Ozek M, Gunel M. Cerebral Venous Malformations Have Distinct Genetic Origin From Cerebral Cavernous Malformations. Stroke 2005, 36: 2479-2480. PMID: 16239636, DOI: 10.1161/01.str.0000183616.99139.d3.Peer-Reviewed Original ResearchMeSH KeywordsApoptosis Regulatory ProteinsBlood VesselsCarrier ProteinsChildDNA Mutational AnalysisExonsFamily HealthFemaleFrameshift MutationGene Expression RegulationHumansIntracranial Arteriovenous MalformationsKRIT1 ProteinMaleMembrane ProteinsMicrotubule-Associated ProteinsModels, GeneticMutationPedigreeProto-Oncogene ProteinsConceptsMutational analysisCerebral cavernous malformationsDistinct genetic originsCCM genesCerebral venous malformationSuch mutationsCausative genesUnique familyFrameshift mutationGenesGenetic originCCM1 geneCommon originMutationsFamilyVenous malformationsPathogenetic mechanismsCavernous malformationsMembersDistinct biologyPDCD10BiologyExon 19KRIT1Different pathogenetic mechanisms
2004
Krev1 interaction trapped-1/cerebral cavernous malformation-1 protein expression during early angiogenesis.
Guzeloglu-Kayisli O, Kayisli UA, Amankulor NM, Voorhees JR, Gokce O, DiLuna ML, Laurans MS, Luleci G, Gunel M. Krev1 interaction trapped-1/cerebral cavernous malformation-1 protein expression during early angiogenesis. Journal Of Neurosurgery 2004, 100: 481-7. PMID: 15287459, DOI: 10.3171/ped.2004.100.5.0481.Peer-Reviewed Original ResearchKRIT1/Cerebral Cavernous Malformation 1 Protein Localizes to Vascular Endothelium, Astrocytes, and Pyramidal Cells of the Adult Human Cerebral Cortex
Guzeloglu-Kayisli O, Amankulor NM, Voorhees J, Luleci G, Lifton RP, Gunel M. KRIT1/Cerebral Cavernous Malformation 1 Protein Localizes to Vascular Endothelium, Astrocytes, and Pyramidal Cells of the Adult Human Cerebral Cortex. Neurosurgery 2004, 54: 943-949. PMID: 15046662, DOI: 10.1227/01.neu.0000114512.59624.a5.Peer-Reviewed Original ResearchMeSH KeywordsAdultAstrocytesBlotting, WesternBrain NeoplasmsCerebral CortexChromosome AberrationsEndothelium, VascularGene Expression Regulation, NeoplasticGenes, DominantHemangioma, CavernousHemangioma, Cavernous, Central Nervous SystemHumansImmunoenzyme TechniquesKRIT1 ProteinMicrotubule-Associated ProteinsProto-Oncogene ProteinsPyramidal CellsConceptsCerebral cavernous malformationsCerebral cortexCavernous malformationsVascular endotheliumCentral nervous system vasculatureAdult human cerebral cortexEndothelial cellsCerebral cavernous malformation lesionsBlood-brain barrierAstrocytic foot processesFamilial cerebral cavernous malformationsHuman cerebral cortexCentral nervous systemAutosomal dominant disorderCerebral angiogenesisPyramidal neuronsPyramidal cellsBlood-organ barriersNervous systemWhite pulpRed pulpIntense stainingWestern blottingFoot processesCardiac myocytes
2003
Mutational analysis of 206 families with cavernous malformations.
Laurans MS, DiLuna ML, Shin D, Niazi F, Voorhees JR, Nelson-Williams C, Johnson EW, Siegel AM, Steinberg GK, Berg MJ, Scott RM, Tedeschi G, Enevoldson TP, Anson J, Rouleau GA, Ogilvy C, Awad IA, Lifton RP, Gunel M. Mutational analysis of 206 families with cavernous malformations. Journal Of Neurosurgery 2003, 99: 38-43. PMID: 12854741, DOI: 10.3171/jns.2003.99.1.0038.Peer-Reviewed Original Research
2002
KRIT1, a gene mutated in cerebral cavernous malformation, encodes a microtubule-associated protein
Gunel M, Laurans MS, Shin D, DiLuna ML, Voorhees J, Choate K, Nelson-Williams C, Lifton RP. KRIT1, a gene mutated in cerebral cavernous malformation, encodes a microtubule-associated protein. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 10677-10682. PMID: 12140362, PMCID: PMC125011, DOI: 10.1073/pnas.122354499.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAortaCattleCells, CulturedCentral Nervous System Vascular MalformationsChlorocebus aethiopsCOS CellsEndothelium, VascularGene ExpressionMicrotubule-Associated ProteinsMicrotubulesMitosisMolecular Sequence DataMutagenesisPrecipitin TestsProto-Oncogene ProteinsRadiographyTubulinConceptsCerebral cavernous malformationsCavernous malformationsCerebral cavernous malformation lesionsMicrotubule-associated proteinsProtein-1 alphaAutosomal dominant diseaseEndothelial tube formationCerebral hemorrhageCerebral capillariesEndothelial cellsDominant diseaseMalformationsTube formationPlus endsSite of cytokinesisSpindle pole bodyEvidence of interactionGene 1Possible roleCell-matrix interactionsKRIT1Late phaseEnds of microtubulesEndothelial cell shapePole body