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Permanent URI for this collectionhttps://hdl.handle.net/11443/932

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Author: search.filters.author.Bayri, Yasar

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    De Novo Mutation in Genes Regulating Neural Stem Cell Fate in Human Congenital Hydrocephalus
    (CELL PRESS, 2018-01-01) Furey, Charuta Gavankar; Choi, Jungmin; Jin, Sheng Chih; Zeng, Xue; Timberlake, Andrew T.; Nelson-Williams, Carol; Mansuri, M. Shahid; Lu, Qiongshi; Duran, Daniel; Panchagnula, Shreyas; Allocco, August; Karimy, Jason K.; Khanna, Arjun; Gaillard, Jonathan R.; DeSpenza, Tyrone; Antwi, Prince; Loring, Erin; Butler, William E.; Smith, Edward R.; Warf, Benjamin C.; Strahle, Jennifer M.; Limbrick, David D.; Storm, Phillip B.; Heuer, Gregory; Jackson, Eric M.; Iskandar, Bermans J.; Johnston, James M.; Tikhonova, Irina; Castaldi, Christopher; Lopez-Giraldez, Francesc; Bjornson, Robert D.; Knight, James R.; Bilguvar, Kaya; Mane, Shrikant; Alper, Seth L.; Haider, Shozeb; Guclu, Bulent; Bayri, Yasar; Sahin, Yener; Apuzzo, Michael L. J.; Duncan, Charles C.; DiLuna, Michael L.; Gunel, Murat; Lifton, Richard P.; Kahle, Kristopher T.
    Congenital hydrocephalus (CH), featuring markedly enlarged brain ventricles, is thought to arise from failed cerebrospinal fluid (CSF) homeostasis and is treated with lifelong surgical CSF shunting with substantial morbidity. CH pathogenesis is poorly understood. Exome sequencing of 125 CH trios and 52 additional probands identified three genes with significant burden of rare damaging de novo or transmitted mutations: TRIM71 (p = 2.15 x 10(-7)), SMARCC1 (p = 8.15 x 10(-10)), and PTCH1 (p = 1.06 x 10(-6)). Additionally, two de novo duplications were identified at the SHH locus, encoding the PTCH1 ligand (p = 1.2 x 10(-4)). Together, these probands account for similar to 10\% of studied cases. Strikingly, all four genes are required for neural tube development and regulate ventricular zone neural stem cell fate. These results implicate impaired neurogenesis (rather than active CSF accumulation) in the pathogenesis of a subset of CH patients, with potential diagnostic, prognostic, and therapeutic ramifications.
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    Hereditary spastic paraplegia with recessive trait caused by mutation in KLC4 gene
    (NATURE PUBLISHING GROUP, 2015-01-01) Bayrakli, Fatih; Poyrazoglu, Hatice Gamze; Yuksel, Sirin; Yakicier, Cengiz; Erguner, Bekir; Sagiroglu, Mahmut Samil; Yuceturk, Betul; Ozer, Bugra; Doganay, Selim; Tanrikulu, Bahattin; Seker, Askin; Akbulut, Fatih; Ozen, Ali; Per, Huseyin; Kumandas, Sefer; Torun, Yasemin Altuner; Bayri, Yasar; Sakar, Mustafa; Dagcinar, Adnan; Ziyal, Ibrahim
    We report an association between a new causative gene and spastic paraplegia, which is a genetically heterogeneous disorder. Clinical phenotyping of one consanguineous family followed by combined homozygosity mapping and whole-exome sequencing analysis. Three patients from the same family shared common features of progressive complicated spastic paraplegia. They shared a single homozygous stretch area on chromosome 6. Whole-exome sequencing revealed a homozygous mutation (c.853\_871del19) in the gene coding the kinesin light chain 4 protein (KLC4). Meanwhile, the unaffected parents and two siblings were heterozygous and one sibling was homozygous wild type. The 19 bp deletion in exon 6 generates a stop codon and thus a truncated messenger RNA and protein. The association of a KLC4 mutation with spastic paraplegia identifies a new locus for the disease.
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    Genomic Analysis of Non-NF2 Meningiomas Reveals Mutations in TRAF7, KLF4, AKT1, and SMO
    (AMER ASSOC ADVANCEMENT SCIENCE, 2013-01-01) Clark, Victoria E.; Erson-Omay, E. Zeynep; Serin, Akdes; Yin, Jun; Cotney, Justin; Oezduman, Koray; Avsar, Timuin; Li, Jie; Murray, Phillip B.; Henegariu, Octavian; Yilmaz, Saliha; Guenel, Jennifer Moliterno; Carrion-Grant, Geneive; Yilmaz, Baran; Grady, Conor; Tanrikulu, Bahattin; Bakircioglu, Mehmet; Kaymakcalan, Hande; Caglayan, Ahmet Okay; Sencar, Leman; Ceyhun, Emre; Atik, A. Fatih; Bayri, Yasar; Bai, Hanwen; Kolb, Luis E.; Hebert, Ryan M.; Omay, S. Bulent; Mishra-Gorur, Ketu; Choi, Murim; Overton, John D.; Holland, Eric C.; Mane, Shrikant; State, Matthew W.; Bilguevar, Kaya; Baehring, Joachim M.; Gutin, Philip H.; Piepmeier, Joseph M.; Vortmeyer, Alexander; Brennan, Cameron W.; Pamir, M. Necmettin; Kilic, Tuerker; Lifton, Richard P.; Noonan, James P.; Yasuno, Katsuhito; Guenel, Murat
    We report genomic analysis of 300 meningiomas, the most common primary brain tumors, leading to the discovery of mutations in TRAF7, a proapoptotic E3 ubiquitin ligase, in nearly one-fourth of all meningiomas. Mutations in TRAF7 commonly occurred with a recurrent mutation ( K409Q) in KLF4, a transcription factor known for its role in inducing pluripotency, or with AKT1(E17K), a mutation known to activate the PI3K pathway. SMO mutations, which activate Hedgehog signaling, were identified in similar to 5\% of non-NF2 mutant meningiomas. These non-NF2 meningiomas were clinically distinctive-nearly always benign, with chromosomal stability, and originating from the medial skull base. In contrast, meningiomas with mutant NF2 and/or chromosome 22 loss were more likely to be atypical, showing genomic instability, and localizing to the cerebral and cerebellar hemispheres. Collectively, these findings identify distinct meningioma subtypes, suggesting avenues for targeted therapeutics.
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    In Vitro Effects of Mesenchymal Stem Cells and Various Agents on Apoptosis of Glioblastoma Cells
    (TURKISH NEUROSURGICAL SOC, 2019-01-01) Tanrikulu, Bahattin; Ziyal, Ibrahim; Bayri, Yasar
    AIM: To investigate a new anti-tumor treatment method using stem cells transfected with specific genes and proteins that induce apoptosis in tumor cells. MATERIAL and METHODS: We used glioblastoma (GBM) cells and human adipose tissue-derived mesenchymal stem cells (AD-MSCs) in this study. The AD-MSCs were transfected with the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). To overcome apoptosis resistance in tumor cells, we used suberoylanilide hydroxamic acid (SAHA) as the histone deacetylase inhibitor and embelin as the X-linked inhibitor of apoptosis protein (XIAP). In addition, we silenced the XIAP gene on GBM cells with the shXIAP plasmid. Following the determination of half-maximal effective concentration (EC50\%) doses of SAHA and embelin, GBM cells were incubated with them for 24 hours. XIAP-silenced and XIAP-non-silenced GBM cells were cultured with TRAIL-non-transfected and TRAIL-transfected stem cells for 24 hours. Viability and cell cycle analysis of all groups were determined using annexin V/propidium iodide and cell cycle method via flow cytometry. RESULTS: TRAIL-transfected AD-MSCs, XIAP silencing, embelin, and SAHA induced apoptosis in GBM cells and decreased their proliferation, whereas TRAIL-non-tranfected AD-MSCs did not. CONCLUSION: Engineered stem cell therapies and molecular studies show promise in developing combination therapies for effective treatment of GBM.