Featured Publications
PPIL4 is essential for brain angiogenesis and implicated in intracranial aneurysms in humans
Barak T, Ristori E, Ercan-Sencicek AG, Miyagishima DF, Nelson-Williams C, Dong W, Jin SC, Prendergast A, Armero W, Henegariu O, Erson-Omay EZ, Harmancı AS, Guy M, Gültekin B, Kilic D, Rai DK, Goc N, Aguilera SM, Gülez B, Altinok S, Ozcan K, Yarman Y, Coskun S, Sempou E, Deniz E, Hintzen J, Cox A, Fomchenko E, Jung SW, Ozturk AK, Louvi A, Bilgüvar K, Connolly ES, Khokha MK, Kahle KT, Yasuno K, Lifton RP, Mishra-Gorur K, Nicoli S, Günel M. PPIL4 is essential for brain angiogenesis and implicated in intracranial aneurysms in humans. Nature Medicine 2021, 27: 2165-2175. PMID: 34887573, PMCID: PMC8768030, DOI: 10.1038/s41591-021-01572-7.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesPeptidyl-prolyl cis-transPathogenesis of IAContribution of variantsCommon genetic variantsVertebrate modelDeleterious mutationsWnt activatorAssociation studiesWhole-exome sequencingSignificant enrichmentGenetic variantsWntAngiogenesis regulatorsMutationsGene mutationsBrain angiogenesisIntracranial aneurysm ruptureJMJD6AngiogenesisCerebrovascular morphologyCerebrovascular integrityIntracerebral hemorrhageAneurysm ruptureVariantsIn silico analysis of the immunological landscape of pituitary adenomas
Yeung JT, Vesely MD, Miyagishima DF. In silico analysis of the immunological landscape of pituitary adenomas. Journal Of Neuro-Oncology 2020, 147: 595-598. PMID: 32236778, PMCID: PMC7261241, DOI: 10.1007/s11060-020-03476-x.Peer-Reviewed Original ResearchConceptsPituitary adenomasImmunological landscapeImmune cellsM2 macrophagesPituitary tumorsAdenoma subtypesSilent pituitary tumorsMemory T cellsImmune cell typesDifferent immunotherapiesHigh CD8Immune infiltratesImmune landscapeSilent tumorsGH tumorsImmunological compositionMacrophage fractionT cellsMast cellsTumor subtypesSolid tumorsSubclinical casesAdenomasTumorsSubtypesAssociations of meningioma molecular subgroup and tumor recurrence
Youngblood MW, Miyagishima DF, Jin L, Gupte T, Li C, Duran D, Montejo JD, Zhao A, Sheth A, Tyrtova E, Özduman K, Iacoangeli F, Peyre M, Boetto J, Pease M, Avşar T, Huttner A, Bilguvar K, Kilic T, Pamir MN, Amankulor N, Kalamarides M, Erson-Omay EZ, Günel M, Moliterno J. Associations of meningioma molecular subgroup and tumor recurrence. Neuro-Oncology 2020, 23: 783-794. PMID: 33068421, PMCID: PMC8099468, DOI: 10.1093/neuonc/noaa226.Peer-Reviewed Original ResearchConceptsDivergent clinical coursesMolecular subgroupsClinical courseClinical outcomesProgression-free survivalExtent of resectionKaplan-Meier analysisLong-term outcomesLow-grade tumorsCox proportional hazardsDistinct clinical outcomesPostoperative radiationIndependent predictorsMale sexRecurrence rateSurveillance imagingTumor recurrencePrevious recurrencesClinical prognosticationKi-67Outcome dataAggressive subgroupRecurrenceElevated recurrenceProportional hazardsSomatic PIK3CA Mutations in Sporadic Cerebral Cavernous Malformations
Peyre M, Miyagishima D, Bielle F, Chapon F, Sierant M, Venot Q, Lerond J, Marijon P, Abi-Jaoude S, Le Van T, Labreche K, Houlston R, Faisant M, Clémenceau S, Boch AL, Nouet A, Carpentier A, Boetto J, Louvi A, Kalamarides M. Somatic PIK3CA Mutations in Sporadic Cerebral Cavernous Malformations. New England Journal Of Medicine 2021, 385: 996-1004. PMID: 34496175, PMCID: PMC8606022, DOI: 10.1056/nejmoa2100440.Peer-Reviewed Original ResearchConceptsSporadic cerebral cavernous malformationCerebral cavernous malformationsFamilial cerebral cavernous malformationsCavernous malformationsTissue samplesSomatic PIK3CA mutationsCentral nervous systemVascular malformationsPIK3CA mutationsMouse modelHarbored mutationsNervous systemPatientsHuman meningiomasMeningiomasCommon genetic driversGenetic causeLesion tissueMalformationsFunction mutationsSomatic mutationsGenetic driversMiceReaction analysisMutationsHormone 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 potentialMeningiomasPatientsTherapyTrialsA systematic review and individual participant data meta-analysis of gonadal steroid hormone receptors in meningioma.
Miyagishima D, Sundaresan V, Gutierrez A, Barak T, Yeung J, Moliterno J, McGuone D, Claus E, Günel M. A systematic review and individual participant data meta-analysis of gonadal steroid hormone receptors in meningioma. Journal Of Neurosurgery 2023, 139: 1638-1647. PMID: 37243565, PMCID: PMC10226381, DOI: 10.3171/2023.3.jns221838.Peer-Reviewed Original ResearchConceptsIndividual participant dataHR statusProgesterone receptorAndrogen receptorEstrogen receptorHormone receptorsFemale patientsParticipant dataSystematic reviewGonadal steroid hormone receptorsRisk of biasGonadal steroid hormonesPubMed literature reviewProper patient stratificationSkull base locationSteroid hormone receptorsHormonal therapyER expressionUnduplicated articlesFemale sexGrade IIndependent associationPatient stratificationConvexity locationStudy heterogeneity
2023
Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas
Youngblood M, Erson-Omay Z, Li C, Najem H, Coșkun S, Tyrtova E, Montejo J, Miyagishima D, Barak T, Nishimura S, Harmancı A, Clark V, Duran D, Huttner A, Avşar T, Bayri Y, Schramm J, Boetto J, Peyre M, Riche M, Goldbrunner R, Amankulor N, Louvi A, Bilgüvar K, Pamir M, Özduman K, Kilic T, Knight J, Simon M, Horbinski C, Kalamarides M, Timmer M, Heimberger A, Mishra-Gorur K, Moliterno J, Yasuno K, Günel M. Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas. Nature Communications 2023, 14: 6279. PMID: 37805627, PMCID: PMC10560290, DOI: 10.1038/s41467-023-41926-y.Peer-Reviewed Original ResearchPleiotropic role of TRAF7 in skull-base meningiomas and 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-Sencicek A, Bilguvar K, Lifton R, Moliterno J, Louvi A, Yuan S, Deniz E, Brueckner M, Gunel M. Pleiotropic role of TRAF7 in skull-base meningiomas and congenital heart disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2214997120. PMID: 37043537, PMCID: PMC10120005, DOI: 10.1073/pnas.2214997120.Peer-Reviewed Original ResearchConceptsWild-type proteinInherited mutationsCardiac outflow tractDevelopmental heart defectsProtein functionLack ciliaPleiotropic rolesMechanistic convergenceNeural crestCiliary defectsSomatic variantsForebrain meningesCommon originDominant mannerMutationsTRAF7ZebrafishMutantsDisparate pathologiesHeterodimerizationKnockdownGeneticsProteinCiliaCongenital heart
2022
Genomic 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
Surgical strategies for older patients with glioblastoma
Barak T, Vetsa S, Nadar A, Jin L, Gupte TP, Fomchenko EI, Miyagishima DF, Yalcin K, Vasandani S, Gorelick E, Zhao AY, Antonios J, Theriault BC, Lifton N, Marianayagam N, Omay B, Omay ZE, Huttner A, McGuone D, Blondin NA, Corbin Z, Fulbright RK, Moliterno J. Surgical strategies for older patients with glioblastoma. Journal Of Neuro-Oncology 2021, 155: 255-264. PMID: 34626296, PMCID: PMC8651607, DOI: 10.1007/s11060-021-03862-z.Peer-Reviewed Original ResearchConceptsKarnofsky performance scoreLength of surgeryOlder patientsOverall survivalPostoperative complicationsSurgical resectionSurgical strategyLow preoperative KPS scorePoor Karnofsky performance scoreLow Karnofsky performance scoreYale-New Haven HospitalPostoperative adjuvant treatmentPreoperative KPS scoreAdjuvant treatment regimensExtent of resectionNew Haven HospitalUse of ioMRIAdjuvant treatmentHospital stayKPS scoreMethodsClinical dataConsecutive patientsPrognostic factorsTreatment regimensExperienced handsDIAPH1 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 hospitalsTargeting the CSF1/CSF1R axis is a potential treatment strategy for malignant meningiomas
Yeung J, Yaghoobi V, Miyagishima D, Vesely MD, Zhang T, Badri T, Nassar A, Han X, Sanmamed MF, Youngblood M, Peyre M, Kalamarides M, Rimm DL, Gunel M, Chen L. Targeting the CSF1/CSF1R axis is a potential treatment strategy for malignant meningiomas. Neuro-Oncology 2021, 23: 1922-1935. PMID: 33914067, PMCID: PMC8563319, DOI: 10.1093/neuonc/noab075.Peer-Reviewed Original ResearchConceptsColony-stimulating factor-1Myeloid cellsMalignant meningiomasTumor microenvironmentCSF1/CSF1RRNA-seqRNA sequencingHuman meningiomasImmune subsetsGene expressionT cellsTreatment strategiesNormalization cancer immunotherapyImportant regulatorCell typesNovel immunocompetent murine modelDeath ligand 1 (PD-L1) expressionCell death receptor-1Immunosuppressive myeloid cellsDeath receptor-1Ligand 1 expressionFactor 1Immune cell typesImmunocompetent murine modelEffective treatment strategies
2020
Clinical and economic burden of neurofibromatosis type 2 in the United States
Koo AB, Yeung JT, Freedman IG, Lee JH, Ahmed OM, Ma AK, Miyagishima DF, DiLuna M, Kahle K. Clinical and economic burden of neurofibromatosis type 2 in the United States. Clinical Neurology And Neurosurgery 2020, 197: 106053. PMID: 32683193, DOI: 10.1016/j.clineuro.2020.106053.Peer-Reviewed Original ResearchConceptsOpen resectionPatient demographicsRisk factorsMeningioma resectionMulti-year cross-sectional studyNeurofibromatosis type 2 (NF2) patientsSpine tumor resectionCommon admission diagnosesNational Inpatient SampleType 2 patientsCross-sectional studySignificant independent associationNeurofibromatosis type 2Regression analysisInflation-adjusted costAdmission diagnosisHospital stayDischarge weightIndependent predictorsObstructive hydrocephalusSurgical interventionDiagnosis codesHospital characteristicsInpatient populationInpatient Sample