Featured Publications
A Founder Mutation as a Cause of Cerebral Cavernous Malformation in Hispanic Americans
Günel M, Awad I, Finberg K, Anson J, Steinberg G, Batjer H, Kopitnik T, Morrison L, Giannotta S, Nelson-Williams C, Lifton R. A Founder Mutation as a Cause of Cerebral Cavernous Malformation in Hispanic Americans. New England Journal Of Medicine 1996, 334: 946-951. PMID: 8596595, DOI: 10.1056/nejm199604113341503.Peer-Reviewed Original ResearchConceptsCavernous malformationsCerebral cavernous malformationsSporadic casesFamilial diseaseSame mutationSporadic cavernous malformationsDevelopment of symptomsHispanic AmericansCerebral hemorrhageVascular diseaseAsymptomatic carriersHigh prevalenceClinical casesMalformationsDiseaseFounder mutationPatientsAge dependenceAffected membersKindredsMarkersMexican descentEthnic groupsMutationsSame allele
2022
Hormone therapies in meningioma-where are we?
Miyagishima D, Moliterno J, Claus E, Günel M. Hormone therapies in meningioma-where are we? Journal Of Neuro-Oncology 2022, 161: 297-308. PMID: 36418843, PMCID: PMC10371392, DOI: 10.1007/s11060-022-04187-1.Peer-Reviewed Original ResearchConceptsPositive receptor statusReceptor statusSomatostatin analoguesClinical trialsHormone-related risk factorsMajority of patientsNIH Clinical Trials DatabaseClinical trials databasesStratification of patientsHormone therapyTrials databasesFuture trialsHormonal agentsSpecific therapyRisk factorsSomatostatin receptorsInclusion criteriaMEDLINE-PubMedMeningioma growthMost meningiomasTherapeutic potentialMeningiomasPatientsTherapyTrialsEPCO-40. INFRATENTORIAL NF2 MUTANT SPORADIC MENINGIOMAS DIFFER FROM THOSE IN SUPRATENTORIAL LOCATIONS AND ARE MORE BENIGN
Vasandani S, Vetsa S, Jalal M, Yalcin K, Marianayagam N, Nadar A, Jin L, Fulbright R, Erson-Omay E, Günel M, Moliterno J. EPCO-40. INFRATENTORIAL NF2 MUTANT SPORADIC MENINGIOMAS DIFFER FROM THOSE IN SUPRATENTORIAL LOCATIONS AND ARE MORE BENIGN. Neuro-Oncology 2022, 24: vii125-vii125. DOI: 10.1093/neuonc/noac209.474.Peer-Reviewed Original ResearchSupratentorial locationWhole-exome sequencing dataHigh-risk clinical featuresLonger progression-free survivalProgression-free survivalExtent of resectionShorter overall survivalDifferent intracranial locationsChromosome 1p deletionOverall survivalClinical featuresInfratentorial tumorsAggressive featuresClinical manifestationsClinical behaviorKi-67Intracranial locationMeningiomasTumorsUnstable tumorsNF2 lossResectionGenomic profilesPatientsExome sequencing dataCross-platform analysis reveals cellular and molecular landscape of glioblastoma invasion
Chen AT, Xiao Y, Tang X, Baqri M, Gao X, Reschke M, Sheu WC, Long G, Zhou Y, Deng G, Zhang S, Deng Y, Bai Z, Kim D, Huttner A, Kunes R, Günel M, Moliterno J, Saltzman WM, Fan R, Zhou J. Cross-platform analysis reveals cellular and molecular landscape of glioblastoma invasion. Neuro-Oncology 2022, 25: 482-494. PMID: 35901838, PMCID: PMC10013636, DOI: 10.1093/neuonc/noac186.Peer-Reviewed Original ResearchConceptsCrystallin alpha BTumor invasionGBM invasionHistology samplesMolecular landscapeTreatment of glioblastomaPostoperative recurrenceGBM patientsInvasive glioblastomaResection modelGlioblastomaNon-invasive counterpartsGBM samplesGlioblastoma invasionCD44PatientsInvasionAlpha BCellular levelTranscriptomic featuresRNA sequencing dataRecurrenceHistology stainsLevelsDiseaseGenomic profiling of sporadic multiple meningiomas
Erson-Omay EZ, Vetsa S, Vasandani S, Barak T, Nadar A, Marianayagam NJ, Yalcin K, Miyagishima D, Aguilera SM, Robert S, Mishra-Gorur K, Fulbright RK, McGuone D, Günel M, Moliterno J. Genomic profiling of sporadic multiple meningiomas. BMC Medical Genomics 2022, 15: 112. PMID: 35568945, PMCID: PMC9107270, DOI: 10.1186/s12920-022-01258-0.Peer-Reviewed Original ResearchConceptsGrade IComprehensive next-generation sequencingMonoclonal originClinical management strategiesPrior radiation exposureRelevant clinical dataMajority of tumorsInter-tumoral heterogeneitySurgical resectionClinical behaviorGrade IIClinical dataFamily historyMultiple meningiomasGrade I.Same patientMonoclonal expansionPatientsClonal formationBilateral meningiomasMeningiomasIndividual tumorsTumorsPatient behavesGenomic profiling
2021
DIAPH1 Variants in Non–East Asian Patients With Sporadic Moyamoya Disease
Kundishora AJ, Peters ST, Pinard A, Duran D, Panchagnula S, Barak T, Miyagishima DF, Dong W, Smith H, Ocken J, Dunbar A, Nelson-Williams C, Haider S, Walker RL, Li B, Zhao H, Thumkeo D, Marlier A, Duy PQ, Diab NS, Reeves BC, Robert SM, Sujijantarat N, Stratman AN, Chen YH, Zhao S, Roszko I, Lu Q, Zhang B, Mane S, Castaldi C, López-Giráldez F, Knight JR, Bamshad MJ, Nickerson DA, Geschwind DH, Chen SL, Storm PB, Diluna ML, Matouk CC, Orbach DB, Alper SL, Smith ER, Lifton RP, Gunel M, Milewicz DM, Jin SC, Kahle KT. DIAPH1 Variants in Non–East Asian Patients With Sporadic Moyamoya Disease. JAMA Neurology 2021, 78: 993-1003. PMID: 34125151, PMCID: PMC8204259, DOI: 10.1001/jamaneurol.2021.1681.Peer-Reviewed Original ResearchConceptsSporadic moyamoya diseaseMoyamoya diseaseValidation cohortDiscovery cohortIntracranial internal carotid arteryRisk genesBilateral moyamoya diseaseTransfusion-dependent thrombocytopeniaLarger validation cohortNon-East Asian patientsInternal carotid arteryAsian individualsCompound heterozygous variantsNon-East AsiansProgressive vasculopathyTransmitted variantsAsian patientsChildhood strokeMedical recordsCarotid arteryTherapeutic ramificationsMAIN OUTCOMEMouse brain tissuePatientsUS hospitals
2020
Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus
Jin SC, Dong W, Kundishora AJ, Panchagnula S, Moreno-De-Luca A, Furey CG, Allocco AA, Walker RL, Nelson-Williams C, Smith H, Dunbar A, Conine S, Lu Q, Zeng X, Sierant MC, Knight JR, Sullivan W, Duy PQ, DeSpenza T, Reeves BC, Karimy JK, Marlier A, Castaldi C, Tikhonova IR, Li B, Peña HP, Broach JR, Kabachelor EM, Ssenyonga P, Hehnly C, Ge L, Keren B, Timberlake AT, Goto J, Mangano FT, Johnston JM, Butler WE, Warf BC, Smith ER, Schiff SJ, Limbrick DD, Heuer G, Jackson EM, Iskandar BJ, Mane S, Haider S, Guclu B, Bayri Y, Sahin Y, Duncan CC, Apuzzo MLJ, DiLuna ML, Hoffman EJ, Sestan N, Ment LR, Alper SL, Bilguvar K, Geschwind DH, Günel M, Lifton RP, Kahle KT. Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus. Nature Medicine 2020, 26: 1754-1765. PMID: 33077954, PMCID: PMC7871900, DOI: 10.1038/s41591-020-1090-2.Peer-Reviewed Original ResearchConceptsCongenital hydrocephalusPoor neurodevelopmental outcomesPost-surgical patientsCerebrospinal fluid accumulationNeural stem cell biologyGenetic disruptionWhole-exome sequencingPrimary pathomechanismEarly brain developmentNeurodevelopmental outcomesHigh morbidityCSF diversionMutation burdenFluid accumulationBrain ventriclesCH casesBrain developmentDe novo mutationsPatientsExome sequencingCSF dynamicsDisease mechanismsHydrocephalusNovo mutationsCell types
2018
Loss of Protocadherin‐12 Leads to Diencephalic‐Mesencephalic Junction Dysplasia Syndrome
Guemez‐Gamboa A, Çağlayan AO, Stanley V, Gregor A, Zaki M, Saleem SN, Musaev D, McEvoy‐Venneri J, Belandres D, Akizu N, Silhavy JL, Schroth J, Rosti RO, Copeland B, Lewis SM, Fang R, Issa MY, Per H, Gumus H, Bayram AK, Kumandas S, Akgumus GT, Erson‐Omay E, Yasuno K, Bilguvar K, Heimer G, Pillar N, Shomron N, Weissglas‐Volkov D, Porat Y, Einhorn Y, Gabriel S, Ben‐Zeev B, Gunel M, Gleeson JG. Loss of Protocadherin‐12 Leads to Diencephalic‐Mesencephalic Junction Dysplasia Syndrome. Annals Of Neurology 2018, 84: 638-647. PMID: 30178464, PMCID: PMC6510237, DOI: 10.1002/ana.25327.Peer-Reviewed Original ResearchConceptsBrainstem malformationDysplasia syndromeEndothelial cellsBiallelic mutationsAutosomal recessive malformationSuch pathogenic variantsCharacteristic clinical presentationPatient-derived induced pluripotent stem cellsWhite matter tractsAnn NeurolAppendicular spasticityBrain calcificationClinical presentationPoor outcomeAxial hypotoniaPsychomotor disabilityProgressive microcephalyTract defectsPathogenic variantsPhenotypic spectrumPatientsCraniofacial dysmorphismBrain imagingNeural precursorsProtein expressionBiallelic loss of human CTNNA2, encoding αN-catenin, leads to ARP2/3 complex overactivity and disordered cortical neuronal migration
Schaffer AE, Breuss MW, Caglayan AO, Al-Sanaa N, Al-Abdulwahed HY, Kaymakçalan H, Yılmaz C, Zaki MS, Rosti RO, Copeland B, Baek ST, Musaev D, Scott EC, Ben-Omran T, Kariminejad A, Kayserili H, Mojahedi F, Kara M, Cai N, Silhavy JL, Elsharif S, Fenercioglu E, Barshop BA, Kara B, Wang R, Stanley V, James KN, Nachnani R, Kalur A, Megahed H, Incecik F, Danda S, Alanay Y, Faqeih E, Melikishvili G, Mansour L, Miller I, Sukhudyan B, Chelly J, Dobyns WB, Bilguvar K, Jamra RA, Gunel M, Gleeson JG. Biallelic loss of human CTNNA2, encoding αN-catenin, leads to ARP2/3 complex overactivity and disordered cortical neuronal migration. Nature Genetics 2018, 50: 1093-1101. PMID: 30013181, PMCID: PMC6072555, DOI: 10.1038/s41588-018-0166-0.Peer-Reviewed Original ResearchConceptsNeuronal migrationHuman cerebral cortexCortical neuronal migrationΒ-catenin signalingCerebral cortexPotential disease mechanismsDevelopmental brain defectsBiallelic truncating mutationsNeuronal phenotypeBiallelic lossBrain defectsBiallelic mutationsTruncating mutationsDisease mechanismsΒ-cateninPachygyriaRecessive formNeurite stabilityNeuronsFamily membersCTNNA2OveractivityPatientsDe Novo Mutation in Genes Regulating Neural Stem Cell Fate in Human Congenital Hydrocephalus
Furey CG, Choi J, Jin SC, Zeng X, Timberlake AT, Nelson-Williams C, Mansuri MS, Lu Q, Duran D, Panchagnula S, Allocco A, Karimy JK, Khanna A, Gaillard JR, DeSpenza T, Antwi P, Loring E, Butler WE, Smith ER, Warf BC, Strahle JM, Limbrick DD, Storm PB, Heuer G, Jackson EM, Iskandar BJ, Johnston JM, Tikhonova I, Castaldi C, López-Giráldez F, Bjornson RD, Knight JR, Bilguvar K, Mane S, Alper SL, Haider S, Guclu B, Bayri Y, Sahin Y, Apuzzo MLJ, Duncan CC, DiLuna ML, Günel M, Lifton RP, Kahle KT. De Novo Mutation in Genes Regulating Neural Stem Cell Fate in Human Congenital Hydrocephalus. Neuron 2018, 99: 302-314.e4. PMID: 29983323, PMCID: PMC7839075, DOI: 10.1016/j.neuron.2018.06.019.Peer-Reviewed Original ResearchConceptsCongenital hydrocephalusNeural stem cell fateHuman congenital hydrocephalusDamaging de novoCerebrospinal fluid homeostasisSubstantial morbidityCH patientsTherapeutic ramificationsSignificant burdenBrain ventriclesCH pathogenesisNeural tube developmentFluid homeostasisDe novo mutationsExome sequencingAdditional probandsHydrocephalusPathogenesisNovo mutationsNovo duplicationProbandsDe novoCell fateMorbidityPatients9p24 triplication in syndromic hydrocephalus with diffuse villous hyperplasia of the choroid plexus
Furey C, Antwi P, Duran D, Timberlake AT, Nelson-Williams C, Matouk CC, DiLuna ML, Günel M, Kahle KT. 9p24 triplication in syndromic hydrocephalus with diffuse villous hyperplasia of the choroid plexus. Molecular Case Studies 2018, 4: a003145. PMID: 29895553, PMCID: PMC6169828, DOI: 10.1101/mcs.a003145.Peer-Reviewed Original ResearchConceptsDiffuse villous hyperplasiaVillous hyperplasiaChoroid plexusSyndromic hydrocephalusCerebrospinal fluid homeostasisSurgical managementPathological featuresHigh prevalenceHydrocephalus treatmentHydrocephalusDVHCPFluid homeostasisCSF productionHyperplasiaPlexusChromosome 9pCritical genesHypersecretionPatientsPathogenesisPrevalenceDisease
2016
Familial occurrence of brain arteriovenous malformation: a novel ACVRL1 mutation detected by whole exome sequencing.
Yılmaz B, Toktaş ZO, Akakın A, Işık S, Bilguvar K, Kılıç T, Günel M. Familial occurrence of brain arteriovenous malformation: a novel ACVRL1 mutation detected by whole exome sequencing. Journal Of Neurosurgery 2016, 126: 1879-1883. PMID: 27611203, DOI: 10.3171/2016.6.jns16665.Peer-Reviewed Original ResearchConceptsBrain arteriovenous malformationsHereditary hemorrhagic telangiectasiaWhole-exome sequencingArteriovenous malformationsExome sequencingWhole-exome sequencing analysisSpinal arteriovenous malformationsDiagnostic classification schemesExome sequencing analysisComprehensive genomic characterizationConclusion Study resultsCranial MRIDirect Sanger sequencingHemorrhagic telangiectasiaBlood samplesFamilial occurrenceHeterozygous mutationsACVRL1 mutationsPatientsThree SiblingsFourth siblingVariant segregationSanger sequencingMalformationsSiblings
2015
CBM-05FUNCTIONAL DIFFERENCES BETWEEN PD-1+ AND PD-1– CD4+ T EFFECTOR CELLS IN HEALTHY DONORS AND PATIENTS WITH GLIOBLASTOMA
Goods B, Lowther D, Lucca L, Hernandez A, Lerner B, Gunel M, Raddassi K, Simon J, Coric V, Love J, Hafler D. CBM-05FUNCTIONAL DIFFERENCES BETWEEN PD-1+ AND PD-1– CD4+ T EFFECTOR CELLS IN HEALTHY DONORS AND PATIENTS WITH GLIOBLASTOMA. Neuro-Oncology 2015, 17: v70-v70. PMCID: PMC4638709, DOI: 10.1093/neuonc/nov211.05.Peer-Reviewed Original ResearchA congenital disorder of deglycosylation: Biochemical characterization of N-glycanase 1 deficiency in patient fibroblasts
He P, Grotzke JE, Ng BG, Gunel M, Jafar-Nejad H, Cresswell P, Enns GM, Freeze HH. A congenital disorder of deglycosylation: Biochemical characterization of N-glycanase 1 deficiency in patient fibroblasts. Glycobiology 2015, 25: 836-844. PMID: 25900930, PMCID: PMC4487302, DOI: 10.1093/glycob/cwv024.Peer-Reviewed Original ResearchMeSH KeywordsBacterial ProteinsDevelopmental DisabilitiesEnzyme AssaysExonsEye Diseases, HereditaryFibroblastsGene ExpressionGenes, ReporterHepatic InsufficiencyHumansLacrimal Apparatus DiseasesLuminescent ProteinsMutationPeptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine AmidasePeripheral Nervous System DiseasesPrimary Cell CultureSeizuresConceptsAbnormal liver functionPatient fibroblastsPeripheral neuropathyLiver functionPatient-derived fibroblastsDevelopmental delayCongenital disorderN-glycanase 1 (NGLY1) deficiencyVenus fluorescencePronounced reductionFibroblastsN-glycanase 1Enzymatic activityMutationsNGLY1NeuropathyPatientsSeizuresAlacrimaActivity
2014
Autosomal recessive spastic tetraplegia caused by AP4M1 and AP4B1 gene mutation: Expansion of the facial and neuroimaging features
Tüysüz B, Bilguvar K, Koçer N, Yalçınkaya C, Çağlayan O, Gül E, Şahin S, Çomu S, Günel M. Autosomal recessive spastic tetraplegia caused by AP4M1 and AP4B1 gene mutation: Expansion of the facial and neuroimaging features. American Journal Of Medical Genetics Part A 2014, 164: 1677-1685. PMID: 24700674, DOI: 10.1002/ajmg.a.36514.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsBrainChildDNA Mutational AnalysisDNA-Binding ProteinsFaciesFemaleGenes, RecessiveGenetic Association StudiesHomozygoteHumansMagnetic Resonance ImagingMaleMutationNeuroimagingPedigreePhenotypeQuadriplegiaRNA-Binding ProteinsSiblingsConceptsAdaptor protein complex 4Tetraplegic cerebral palsySevere intellectual disabilitySpastic tetraplegiaCerebral palsySpastic tetraplegic cerebral palsyIntellectual disabilityStereotypic laughterCranial imaging findingsWhite matter volumeWhole-exome sequencingNovel homozygous mutationAsymmetrical ventriculomegalyCranial MRIImaging findingsClinical findingsNeuroimaging featuresBrain abnormalitiesCommon findingCorpus callosumAutosomal recessive phenotypePairs of siblingsPatientsSimilar facial featuresMatter volume
2013
Vessel Wall Magnetic Resonance Imaging Identifies the Site of Rupture in Patients With Multiple Intracranial AneurysmsProof of Principle
Matouk CC, Mandell DM, Günel M, Bulsara KR, Malhotra A, Hebert R, Johnson MH, Mikulis DJ, Minja FJ. Vessel Wall Magnetic Resonance Imaging Identifies the Site of Rupture in Patients With Multiple Intracranial AneurysmsProof of Principle. Neurosurgery 2013, 72: 492-496. PMID: 23151622, DOI: 10.1227/neu.0b013e31827d1012.Peer-Reviewed Original ResearchConceptsAneurysmal subarachnoid hemorrhageSite of ruptureSubarachnoid hemorrhageMultiple intracranial aneurysmsMR-VWIHigh-resolution magnetic resonance vessel wall imagingIntracranial aneurysmsSteno-occlusive cerebrovascular diseaseVessel wall magnetic resonance imagingMR imaging findingsVessel wall enhancementMagnetic resonance vessel wall imagingMagnetic resonance imagingVessel wall imagingDefinitive treatmentCerebrovascular diseaseImaging findingsMedical recordsRuptured aneurysmsUnruptured aneurysmsPatientsAneurysmsWall enhancementResonance imagingRupture
2007
Apparently novel genetic syndrome of pachygyria, mental retardation, seizure, and arachnoid cysts
Guzel A, Tatli M, Bilguvar K, DiLuna ML, Bakkaloglu B, Ozturk AK, Bayrakli F, Gunel M. Apparently novel genetic syndrome of pachygyria, mental retardation, seizure, and arachnoid cysts. American Journal Of Medical Genetics Part A 2007, 143A: 672-677. PMID: 17343267, DOI: 10.1002/ajmg.a.31640.Peer-Reviewed Original ResearchConceptsArachnoid cystCerebral anomaliesMental retardationAutosomal recessive inheritanceSeizure disorderNovel genetic syndromeCentrum semiovaleLack of mutationsPerivascular spacesWhite matterNew syndromeGenetic syndromesLissencephaly geneSyndromeCystsRecessive inheritancePachygyriaSeizuresConsanguineous familyRetardationNew phenotypesPatientsGENETICS OF INTRACRANIAL ANEURYSMS
Nahed BV, Bydon M, Ozturk AK, Bilguvar K, Bayrakli F, Gunel M. GENETICS OF INTRACRANIAL ANEURYSMS. Neurosurgery 2007, 60: 213-226. PMID: 17290171, DOI: 10.1227/01.neu.0000249270.18698.bb.Peer-Reviewed Original ResearchConceptsIntracranial aneurysmsRisk factorsPatient-specific risk factorsGenetic susceptibilityAneurysmal subarachnoid hemorrhageHigh-risk individualsSpecific risk factorsIA pathogenesisNovel therapeutic strategiesRupture of aneurysmsDiagnosis of IAAsymptomatic patientsMedical comorbiditiesFormation of IAsPoor prognosisSubarachnoid hemorrhageEarly diagnosisEpidemiological studiesTherapeutic strategiesPreclinical settingDisease pathophysiologyOverall outcomePatientsAneurysmsModest improvement
2000
Carotid Endarterectomy Prevention Strategies and Complications Management
Gunel M, Awad I. Carotid Endarterectomy Prevention Strategies and Complications Management. Neurosurgery Clinics Of North America 2000, 11: 351-364. PMID: 10733850, DOI: 10.1016/s1042-3680(18)30137-2.Peer-Reviewed Original ResearchConceptsCarotid endarterectomyAppropriate patient selectionCarotid occlusive diseaseLow complication ratePerioperative complicationsPerioperative courseComplication rateIntraoperative complicationsOcclusive diseaseSurgical treatmentPatient selectionPostoperative careComplication managementPrevention strategiesCareful assessmentComplicationsEndarterectomyMorbidityPatientsDiseaseCarePrevention
1998
Molecular Biology of Cerebrovascular Diseases
Gunel M, Awad I, Lifton R. Molecular Biology of Cerebrovascular Diseases. 1998, 163-173. DOI: 10.1007/978-1-4613-9350-4_15.Peer-Reviewed Original ResearchMolecular biologyIdentification of genesCerebrovascular diseaseMolecular geneticsMolecular mechanismsScope of neurosurgeryNovel therapeutic strategiesBiologyNew insightsPathologic angiogenesisInherited predispositionTherapeutic strategiesBasic mechanismsPreclinical diagnosisDiseaseGenesGeneticsMechanismAngiogenesisIschemiaPatientsPathophysiologyPathogenesisNew opportunitiesDiagnosis