Featured Publications
Combined HMG-COA reductase and prenylation inhibition in treatment of CCM
Nishimura S, Mishra-Gorur K, Park J, Surovtseva YV, Sebti SM, Levchenko A, Louvi A, Gunel M. Combined HMG-COA reductase and prenylation inhibition in treatment of CCM. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 5503-5508. PMID: 28500274, PMCID: PMC5448170, DOI: 10.1073/pnas.1702942114.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAstrocytesDiphosphonatesDrosophilaDrug Evaluation, PreclinicalDrug Therapy, CombinationEndothelial CellsFatty Acids, MonounsaturatedFemaleFluvastatinHemangioma, Cavernous, Central Nervous SystemHigh-Throughput Screening AssaysHydroxymethylglutaryl-CoA Reductase InhibitorsImidazolesIndolesMaleMAP Kinase Signaling SystemMicePregnancyProtein PrenylationZoledronic AcidConceptsCerebral cavernous malformationsTreatment of CCMsCommon vascular anomaliesPotential pharmacological treatment optionsFocal neurological deficitsPharmacological treatment optionsCCM diseaseAcute mouse modelCentral nervous systemNeurological deficitsHemorrhagic strokePharmacological therapyLesion burdenVascular deficitsSymptomatic lesionsCombination therapyTreatment optionsVascular anomaliesGlial cellsCavernous malformationsMouse modelPrimary astrocytesNervous systemDrug AdministrationSustained inhibition
2016
Biallelic Mutations in TMTC3, Encoding a Transmembrane and TPR-Containing Protein, Lead to Cobblestone Lissencephaly
Jerber J, Zaki MS, Al-Aama JY, Rosti RO, Ben-Omran T, Dikoglu E, Silhavy JL, Caglar C, Musaev D, Albrecht B, Campbell KP, Willer T, Almuriekhi M, Çağlayan A, Vajsar J, Bilgüvar K, Ogur G, Jamra R, Günel M, Gleeson JG. Biallelic Mutations in TMTC3, Encoding a Transmembrane and TPR-Containing Protein, Lead to Cobblestone Lissencephaly. American Journal Of Human Genetics 2016, 99: 1181-1189. PMID: 27773428, PMCID: PMC5097947, DOI: 10.1016/j.ajhg.2016.09.007.Peer-Reviewed Original ResearchConceptsCongenital muscular dystrophyCobblestone lissencephalyOvermigration of neuronsBiallelic mutationsMuscular dystrophyTMTC3Affected individualsWalker-Warburg syndromeMembrane componentsSevere brain malformationsBasement membrane componentsFukuyama congenital muscular dystrophyMuscle creatine phosphokinaseEye defectsMutationsGenesRecessive formGenetic disordersGlial cellsMinimal eyeMuscle involvementCortical dysplasiaBrain malformationsEye anomaliesCreatine phosphokinase
2013
Mutations in LAMB1 Cause Cobblestone Brain Malformation without Muscular or Ocular Abnormalities
Radmanesh F, Caglayan AO, Silhavy JL, Yilmaz C, Cantagrel V, Omar T, Rosti B, Kaymakcalan H, Gabriel S, Li M, Šestan N, Bilguvar K, Dobyns WB, Zaki MS, Gunel M, Gleeson JG. Mutations in LAMB1 Cause Cobblestone Brain Malformation without Muscular or Ocular Abnormalities. American Journal Of Human Genetics 2013, 92: 468-474. PMID: 23472759, PMCID: PMC3591846, DOI: 10.1016/j.ajhg.2013.02.005.Peer-Reviewed Original ResearchConceptsBrain malformationsCongenital muscular dystrophyOcular abnormalitiesPial surfaceWhite matter signal abnormalitiesNeuronal migration disordersRadial glial cellsPial basement membraneLaminin subunit beta-1Brainstem hypoplasiaFirst cortical layerSignal abnormalitiesCerebellar dysplasiaGlial cellsMigration disordersMuscular abnormalitiesOccipital encephaloceleCortical layersBrain diseasesAbnormalitiesHomozygous deleterious mutationMalformationsBeta 1Muscular dystrophyAffected individuals
2011
CCM2 expression during prenatal development and adult human neocortex
Tanriover G, Sozen B, Gunel M, Demir N. CCM2 expression during prenatal development and adult human neocortex. International Journal Of Developmental Neuroscience 2011, 29: 509-514. PMID: 21569831, DOI: 10.1016/j.ijdevneu.2011.04.006.Peer-Reviewed Original ResearchConceptsAdult human neocortexCerebral cavernous malformationsHuman neocortexNeuroglial precursor cellsPrenatal developmentMeans of immunohistochemistryCentral nervous systemWestern blot analysisHuman brain developmentVascular malformationsAdult neocortexGlial cellsCavernous malformationsCCM lesionsVascular endotheliumNervous systemVascular channelsBlood vessel formationArterial endotheliumBrain developmentNeocortexExpression patternsEndotheliumPrecursor cellsCCM loci