2025
Characterizing Stroke Clots Using Single-Cell Sequencing.
Renedo D, Barak T, DeLong J, Acosta J, Sujijantarat N, Koo A, Rivier C, Clocchiatti-Tuozzo S, Huo S, Antonios J, Giles J, Falcone G, Sheth K, Hebert R, Gunel M, Sansing L, Navaratnam D, Matouk C. Characterizing Stroke Clots Using Single-Cell Sequencing. Journal Of The American Heart Association 2025, 14: ejaha2025041738t. PMID: 40878981, DOI: 10.1161/jaha.125.041738.Peer-Reviewed Original ResearchConceptsMulti-marker analysisGene expressionMulti-marker Analysis of GenoMic AnnotationCell type-specific gene expressionT cellsGenome-wide association studiesGene expression of cellsSingle-cell RNA sequencingPotential biomarkersTIMP1Genes associated with atherosclerosisHLA-DRB1*01Single-cell sequencingExpression of genesUpregulated expression of genesGene expression profilesCarotid atherosclerosisGenome annotationCD8 T cellsUpregulated expressionImmune cell compositionAssociation studiesNatural killer cellsImmune cell populationsLarge vessel occlusion strokeO-056 SLAMF1 and non-traumatic subarachnoid hemorrhage: a multi-omics investigation of risk
Renedo D, Koo A, Sujijantarat N, Clocchiatti-Tuozzo S, Huo S, Acosta J, Hebert R, Gunel M, Sansing L, Sheth K, Falcone G, Rivier C, Matouk C. O-056 SLAMF1 and non-traumatic subarachnoid hemorrhage: a multi-omics investigation of risk. 2025, a48.2-a49. DOI: 10.1136/jnis-2025-snis.56.Peer-Reviewed Original ResearchPosterior parasagittal meningiomas display aggressive features independent of size: a multicenter analysis
Koçyiğit S, Chavez M, Orhun Ö, O’Brien J, Inan A, Yaşar A, Dinçer A, Moliterno J, Günel M, Pamir M, Özduman K, Erşen-Danyeli A. Posterior parasagittal meningiomas display aggressive features independent of size: a multicenter analysis. Journal Of Neuro-Oncology 2025, 175: 101-110. PMID: 40569492, PMCID: PMC12367906, DOI: 10.1007/s11060-025-05103-z.Peer-Reviewed Original ResearchConceptsParasagittal meningiomaAnatomical locationKi67 indexWHO-gradeAggressive featuresTumor volume ratioChromosome 1p lossGrading criteriaResultsTumor volumeLarge meningiomasHistological subtypesAggressive biologyHistological gradeMolecular subsetsMulticenter analysisCohort BMeningioma sizeMitotic countRadiological featuresTumor behaviorRisk stratificationBrain invasionRetrospective analysisHistopathological markersIndependent cohortChromosome 1p Loss and 1q Gain for Grading of Meningioma
Landry A, Wang J, Patil V, Liu J, Gui C, Ellenbogen Y, Ajisebutu A, Yefet L, Wei Q, Singh O, Sosa J, Mansouri S, Cohen-Gadol A, Tabatabai G, Tatagiba M, Behling F, Barnholtz-Sloan J, Sloan A, Chotai S, Chambless L, Mansouri A, Makarenko S, Yip S, Ehret F, Capper D, Tsang D, Moliterno J, Gunel M, Wesseling P, Sahm F, Aldape K, Gao A, Zadeh G, Nassiri F. Chromosome 1p Loss and 1q Gain for Grading of Meningioma. JAMA Oncology 2025, 11: 644-649. PMID: 40178835, PMCID: PMC11969356, DOI: 10.1001/jamaoncol.2025.0329.Peer-Reviewed Original ResearchConceptsClassification of central nervous system tumorsChromosomal copy number alterationsProgression-free survivalChromosome 1p lossCopy number alterationsLoss of chromosome 1pGrading of meningiomasWHO gradeWorld Health OrganizationChromosome 1pWorld Health Organization grade 1 meningiomasWorld Health Organization grade 1 tumorWorld Health Organization grade 2 tumorsGain of chromosome 1qHomozygous deletion of CDKN2AAssociated with significantly worse outcomesCentral nervous system tumorsHistopathological diagnosis of meningiomaGrade 3 tumorsGrade 1 tumorsGrade 2 tumorsLoss of 1pGrade 1 meningiomasOutcomes of patientsDeletion of CDKN2AImpact of Social Determinants of Health on Outcomes of Nontraumatic Subarachnoid Hemorrhage
Renedo D, Rivier C, Koo A, Clocchiatti‐Tuozzo S, Huo S, Sujijantarat N, Torres‐Lopez V, Hebert R, Schwamm L, de Havenon A, Gunel M, Matouk C, Falcone G, Sheth K. Impact of Social Determinants of Health on Outcomes of Nontraumatic Subarachnoid Hemorrhage. Journal Of The American Heart Association 2025, 14: e037199. PMID: 40194963, PMCID: PMC12132901, DOI: 10.1161/jaha.124.037199.Peer-Reviewed Original ResearchConceptsSocial determinants of healthSocial deprivation indexDeterminants of healthImpact of social determinants of healthDeprivation indexLength of stayInfluence of social determinants of healthOdds ratioDischarge dispositionHigher social deprivation indexAssociated with reduced oddsAverage length of stayVascular risk factorsAssociated with longer lengthSocial determinantsSignificant health burdenEstimate associationsIn-Hospital DeathNontraumatic subarachnoid hemorrhageSocioeconomic levelHealth burdenOverall mortality rateDecreased deathRisk factorsHealth126 Intracranial Aneurysm Progression and Rupture States Correlate with Dynamic Aneurysmal Immune Landscape
Antonios J, Gultekin B, Theriault B, Yalcin K, Miyagishima D, Sujijantarat N, Koo A, Haynes J, Nowicki K, Hebert R, Barak T, Matouk C, Gunel M. 126 Intracranial Aneurysm Progression and Rupture States Correlate with Dynamic Aneurysmal Immune Landscape. Neurosurgery 2025, 71: 25-25. DOI: 10.1227/neu.0000000000003360_126.Peer-Reviewed Original ResearchRuptured IAMultivariate logistic regression analysisUnruptured IACD4 T cellsImmune cell subsetsImmune cell populationsAneurysm growth rateImmune cell behaviorLogistic regression analysisImmune cell polarizationNon-invasive strategyImmune signaturesGenes related to immune responseImmune landscapeCell subsetsImmune pathophysiologyImmune profileT cellsImmunological markersAntigen presentationAneurysm progressionImmune cascadePoor morbidityPublic health challengeImmune responsePTEN mutations impair CSF dynamics and cortical networks by dysregulating periventricular neural progenitors
DeSpenza T, Kiziltug E, Allington G, Barson D, McGee S, O’Connor D, Robert S, Mekbib K, Nanda P, Greenberg A, Singh A, Duy P, Mandino F, Zhao S, Lynn A, Reeves B, Marlier A, Getz S, Nelson-Williams C, Shimelis H, Walsh L, Zhang J, Wang W, Prina M, OuYang A, Abdulkareem A, Smith H, Shohfi J, Mehta N, Dennis E, Reduron L, Hong J, Butler W, Carter B, Deniz E, Lake E, Constable R, Sahin M, Srivastava S, Winden K, Hoffman E, Carlson M, Gunel M, Lifton R, Alper S, Jin S, Crair M, Moreno-De-Luca A, Luikart B, Kahle K. PTEN mutations impair CSF dynamics and cortical networks by dysregulating periventricular neural progenitors. Nature Neuroscience 2025, 28: 536-557. PMID: 39994410, PMCID: PMC12038823, DOI: 10.1038/s41593-024-01865-3.Peer-Reviewed Original ResearchConceptsNeural progenitor cellsCongenital hydrocephalusCSF dynamicsIncreased CSF productionDe novo mutationsFrequent monogenic causeEverolimus treatmentCSF shuntingNonsurgical treatmentPTEN mutationsAqueductal stenosisInhibitory interneuronsVentriculomegalyProgenitor cellsChoroid plexusMonogenic causeCortical networksIncreased SurvivalBrain ventriclesCortical deficitsNeural progenitorsGene PTENCSF productionNkx2.1PTENSomatic Loss of BCLAF-1 in an Encephalocele Secondary to Idiopathic Intracranial Hypertension
Lau Z, Alanya H, Rimmer R, Gunel M, Omay S, Omay E. Somatic Loss of BCLAF-1 in an Encephalocele Secondary to Idiopathic Intracranial Hypertension. Journal Of Neurological Surgery Part B Skull Base 2025, 86: s1-s576. DOI: 10.1055/s-0045-1803586.Peer-Reviewed Original ResearchSomatic SMARCB1 mutation in spinal meningioma represents branched evolution in a patient with multiple sporadic meningiomas
Gupta M, Samiappan S, Alanya H, Yalcin K, Gultekin B, Sharaf R, Elsamadicy A, Figuera D, Samuel N, Mishra-Gorur K, Kolb L, McGuone D, Gunel M, Erson-Omay E, Moliterno J, Mendel E. Somatic SMARCB1 mutation in spinal meningioma represents branched evolution in a patient with multiple sporadic meningiomas. Neuro-Oncology Advances 2025, 7: vdaf067. PMID: 40386121, PMCID: PMC12081948, DOI: 10.1093/noajnl/vdaf067.Peer-Reviewed Original ResearchDysregulation of mTOR signalling is a converging mechanism in lissencephaly
Zhang C, Liang D, Ercan-Sencicek A, Bulut A, Cortes J, Cheng I, Henegariu O, Nishimura S, Wang X, Peksen A, Takeo Y, Caglar C, Lam T, Koroglu M, Narayanan A, Lopez-Giraldez F, Miyagishima D, Mishra-Gorur K, Barak T, Yasuno K, Erson-Omay E, Yalcinkaya C, Wang G, Mane S, Kaymakcalan H, Guzel A, Caglayan A, Tuysuz B, Sestan N, Gunel M, Louvi A, Bilguvar K. Dysregulation of mTOR signalling is a converging mechanism in lissencephaly. Nature 2025, 638: 172-181. PMID: 39743596, PMCID: PMC11798849, DOI: 10.1038/s41586-024-08341-9.Peer-Reviewed Original ResearchP53-induced death domain protein 1Miller-Dieker lissencephaly syndromeMolecular mechanismsDysregulation of protein translationDysregulation of mTOR signalingDomain protein 1Activity of mTOR complexesMTOR pathwayRelevant molecular mechanismsProtein translationHuman lissencephalyClinically relevant molecular mechanismsRecessive mutationsRare mutationsMiller-DiekerGene expressionCerebral cortex developmentMTOR complexesSpectrum disorderMolecular defectsMTOR signalingCongenital brain malformationsProtein 1GeneticsAssociated with epilepsy
2024
EPCO-35. GENOMIC CHARACTERIZATION OF GROWTH HORMONE SECRETING PITUITARY ADENOMAS
Alanya H, Yalcin K, Hilton B, Gultekin B, Mishra-Gorur K, McGuone D, Gunel M, Omay S, Erson-Omay Z. EPCO-35. GENOMIC CHARACTERIZATION OF GROWTH HORMONE SECRETING PITUITARY ADENOMAS. Neuro-Oncology 2024, 26: viii9-viii9. PMCID: PMC11553213, DOI: 10.1093/neuonc/noae165.0034.Peer-Reviewed Original ResearchGH-secreting pituitary adenomasWhole-exome sequencingPituitary adenomasGNAS mutationsCopy number variationsSporadic GH-secreting pituitary adenomasGrowth hormone (GH)-secreting pituitary adenomasGenomic profilingGrowth hormone secreting pituitary adenomaSecreting pituitary adenomasBlood samplesComprehensive genomic characterizationSomatic GNAS mutationsSingle nucleotide variantsMatched blood samplesGenomic instabilityAssessment of genomic instabilityStatistically significant differenceTumor sizeClinical featuresTumor samplesClinical dataTumorExome sequencingBrain tumorsExploring Molecular and Phenotypic Characteristics of NAGLU Arg234Gly and Asp312Asn Variants
Celebiler H, Barak T, K. D, Kaya I, Erbilgin S, Uytun M, Oztop D, Gumus H, Per H, Ceylaner S, Bozkurt I, Kontaridis M, Bilguvar K, Akhun N, Kilincaslan A, Caglayan A, Erson-Omay E, Gunel M, Ercan-Sencicek A. Exploring Molecular and Phenotypic Characteristics of NAGLU Arg234Gly and Asp312Asn Variants. Molecular Syndromology 2024, 16: 342-353. PMID: 40771184, PMCID: PMC12324730, DOI: 10.1159/000542367.Peer-Reviewed Original ResearchWhole-exome sequencingStandard Sanger sequencingMucopolysaccharidosis type IIIBExome sequencingProgressive neurodegenerative disorderConsanguineous familySanger sequencingNAGLU genePhenotypic characteristicsMagnetic resonance imagingEnzymatic assayNeurodegenerative disordersAffected individualsLoss of activityNeurodegenerative symptomsAutosomal recessive lysosomal disorderCellular mechanismsVariantsLysosomal disorderEnzymeNormal MRI findingsSequenceMPS IIIBMRI findingsType IIIbCC2D1A causes ciliopathy, intellectual disability, heterotaxy, renal dysplasia, and abnormal CSF flow
Kim A, Sakin I, Viviano S, Tuncel G, Aguilera S, Goles G, Jeffries L, Ji W, Lakhani S, Kose C, Silan F, Oner S, Kaplan O, Group M, Ergoren M, Mishra-Gorur K, Gunel M, Sag S, Temel S, Deniz E. CC2D1A causes ciliopathy, intellectual disability, heterotaxy, renal dysplasia, and abnormal CSF flow. Life Science Alliance 2024, 7: e202402708. PMID: 39168639, PMCID: PMC11339347, DOI: 10.26508/lsa.202402708.Peer-Reviewed Original ResearchConceptsDevelopmental disabilitiesIntellectual disabilityPatient-derived fibroblastsMidbrain regionsBrain developmentDefective ciliogenesisCSF circulationDisabilityCSF flowAbnormal CSF flowNervous system developmentMutant tadpolesCiliated tissuesMultiple model systemsVariant functionPronephric ductUnrelated familiesCC2D1AExpression patternsCiliogenesisRenal dysplasiaLeft-right organizerFunctional analysisDisease mechanismsBrain184 PTEN Mutations Portend Cerebral Ventriculomegaly With Autism-Like Deficits in Cortical Circuitry
DeSpenza T, Kizlitug E, Allington G, Barson D, O'Connor D, Robert S, Mekbib K, Singh A, Phan D, Nanda P, Mandino F, Constable T, Lake E, Carter B, Gunel M, Lifton R, Luikart B, Kahle K. 184 PTEN Mutations Portend Cerebral Ventriculomegaly With Autism-Like Deficits in Cortical Circuitry. Neurosurgery 2024, 70: 46-46. DOI: 10.1227/neu.0000000000002809_184.Peer-Reviewed Original ResearchWhole-exome sequencingFetal ventriculomegalyCongenital hydrocephalusExome sequencingChoroid plexus hyperplasiaMutated genesCa2+ imagingMutant mouse modelsPTEN mutantsHuman fetal brainPten mutant miceSporadic CHCerebral ventriculomegalyCSF diversionObstructive hydrocephalusCH patientsCSF secretionPharmacological mTORC1 inhibitionNeurodevelopmental assessmentRadiographic biomarkersFetal brainPTEN mutationsAqueductal stenosisPTEN deletionVentriculomegaly306 Endothelial Infiltrating Regulatory B Cells and NK T Cells Precipitate Inflammatory Cascade That Leads to Aneurysmal Rupture
Antonios J, Barak T, Gultekin B, Yalcin K, Adenu-Mensah N, Sujijantarat N, Koo A, Haynes J, Hebert R, Matouk C, Gunel M. 306 Endothelial Infiltrating Regulatory B Cells and NK T Cells Precipitate Inflammatory Cascade That Leads to Aneurysmal Rupture. Neurosurgery 2024, 70: 88-89. DOI: 10.1227/neu.0000000000002809_306.Peer-Reviewed Original ResearchRegulatory B cellsB cellsSentinel hemorrhageNK cellsInflammatory cascadeCytotoxic CD8 T cellsRecruitment of NK cellsCD8 T cellsAdjunctive immune therapyEndovascular coil embolizationCoordinated immune responseIntracranial aneurysm developmentImmune therapyRecurrent aneurysmsAneurysmal vessel wallT cellsCoil embolizationRuptured aneurysmsTime of ruptureAneurysm ruptureUnruptured aneurysmsInfiltrating populationPatient populationImmune responseAneurysm developmentHeterozygous CDKN2A Loss is Associated with Recurrence and Survival in High, But Not Low Grade Meningiomas
Tabor J, O'Brien J, Valero S, Pappajohn A, McGuone D, Erson-Omay Z, Yasuno K, Gunel M, Moliterno J. Heterozygous CDKN2A Loss is Associated with Recurrence and Survival in High, But Not Low Grade Meningiomas. Neurosurgery 2024, 70: 203-203. DOI: 10.1227/neu.0000000000002810_112.Peer-Reviewed Original ResearchProgression-free survivalHigh-grade meningiomasOverall survivalNF2 mutationsDecreased PFSLow grade meningiomasWHO grading criteriaLow-grade meningiomasAssociated with recurrenceSomatic NF2 mutationsHigher recurrence rateSomatic driver mutationsAggressive clinical characteristicsIncreased chromosomal instabilityLoss of CDKN2A/BHigh-copy number variationCDKN2A mutationsCopy number variationsAggressive meningiomasLow-grade onesProliferative indexCDKN2A lossGrade meningiomasRecurrence rateMitotic countVariations in the genomic profiles and clinical behavior of meningioma by racial and ethnic group.
Tabor J, Dincer A, O'Brien J, Lei H, Vetsa S, Vasandani S, Jalal M, Yalcin K, Morales-Valero S, Marianayagam N, Alanya H, Elsamadicy A, Millares Chavez M, Aguilera S, Mishra-Gorur K, McGuone D, Fulbright R, Jin L, Erson-Omay E, Günel M, Moliterno J. Variations in the genomic profiles and clinical behavior of meningioma by racial and ethnic group. Journal Of Neurosurgery 2024, 141: 664-672. PMID: 38518289, DOI: 10.3171/2024.1.jns231633.Peer-Reviewed Original ResearchBlack patientsSporadic meningiomasClinical outcomesGenomic profilingClinical behavior of meningiomasShorter progression-free survivalAnterior skull base tumorsClinical data of patientsHispanic patientsProgression-free survivalChromosome 1p deletionBehavior of meningiomasIncreased recurrence rateRate of recurrenceSkull base tumorsData of patientsSomatic driver mutationsNon-black patientsShorter PFSOverall survivalAggressive meningiomasTRAF7 mutationsIntracranial meningiomasMeningioma resectionNon-black groupReply to Pisan et al.: Pathogenicity of inherited TRAF7 mutations in congenital heart disease
Mishra-Gorur K, Barak T, Kaulen L, Henegariu O, Jin S, Aguilera S, Yalbir E, Goles G, Nishimura S, Miyagishima D, Djenoune L, Altinok S, K. D, Viviano S, Prendergast A, Zerillo C, Ozcan K, Baran B, Sencar L, Goc N, Yarman Y, Ercan-encicek A, Bilguvar K, Lifton R, Moliterno J, Louvi A, Yuan S, Deniz E, Brueckner M, Gunel M. Reply to Pisan et al.: Pathogenicity of inherited TRAF7 mutations in congenital heart disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2319578121. PMID: 38466853, PMCID: PMC10963000, DOI: 10.1073/pnas.2319578121.Commentaries, Editorials and LettersAPOE ε4 and Intracerebral Hemorrhage in Patients With Brain Arteriovenous Malformation
Renedo D, Rivier C, Koo A, Sujijantarat N, Clocchiatti-Tuozzo S, Wu K, Torres-Lopez V, Huo S, Gunel M, de Havenon A, Sheth K, Matouk C, Falcone G. APOE ε4 and Intracerebral Hemorrhage in Patients With Brain Arteriovenous Malformation. JAMA Network Open 2024, 7: e2355368. PMID: 38363572, PMCID: PMC10873768, DOI: 10.1001/jamanetworkopen.2023.55368.Peer-Reviewed Original ResearchConceptsApolipoprotein E e4Participants of European ancestryRisk of intracerebral hemorrhageHigh risk of intracerebral hemorrhageCross-sectional studyUK BiobankEuropean ancestryHigh riskUs Research ProgramUK Biobank participantsInternational Classification of DiseasesAssociated with higher risk of ICHCross-sectional study of patientsAPOE e4 statusClassification of diseasesApolipoprotein ENinth Revision and Tenth RevisionAssociated with higher riskIndividual-level dataMultivariate logistic regressionIntracerebral hemorrhage riskBrain arteriovenous malformationsIntracerebral hemorrhageBiobank participantsTenth Revision
2023
EPCO-47. HETEROZYGOUS CDKN2A LOSS IS ASSOCIATED WITH HIGHER RECURRENCE AND LOWER SURVIVAL IN HIGH-, BUT NOT LOW-GRADE MENINGIOMAS
Tabor J, Chavez M, O'Brien J, Morales-Valero S, Pappajohn A, McGuone D, Erson-Omay Z, Yasuno K, Gunel M, Moliterno J. EPCO-47. HETEROZYGOUS CDKN2A LOSS IS ASSOCIATED WITH HIGHER RECURRENCE AND LOWER SURVIVAL IN HIGH-, BUT NOT LOW-GRADE MENINGIOMAS. Neuro-Oncology 2023, 25: v134-v135. PMCID: PMC10639255, DOI: 10.1093/neuonc/noad179.0509.Peer-Reviewed Original ResearchProgression-free survivalShorter progression-free survivalHigh recurrence rateHigh-grade meningiomasCDKN2A/BOverall survivalRecurrence rateLow-grade meningiomasHeterozygous lossNF2 mutationsHigh mitotic countFree survivalMethods ClinicalSomatic NF2 mutationsClinical associationsLower OSHigh recurrenceLow-grade onesProliferative indexMitotic countAggressive meningiomasClinical implicationsMeningiomasPotential associationSkull base
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