基本情報
- 所属
- 自治医科大学 分子病態治療研究センター 遺伝子治療研究部 講師
- 学位
- 医学博士(岡山大学大学院)
- J-GLOBAL ID
- 201301061949126420
- researchmap会員ID
- 7000006422
研究分野
1経歴
4-
2016年 - 現在
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2014年 - 2015年
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2013年 - 2014年
学歴
2-
- 2008年
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- 2001年
受賞
2-
2017年
論文
44-
Molecular neurobiology 2024年4月27日 査読有り筆頭著者責任著者It is established that neurogenesis of dentate gyrus is increased after ischemic insult, although the regulatory mechanisms have not yet been elucidated. In this study, we focused on Ezh2 which suppresses gene expression through catalyzing trimethylation of lysine 27 of histone 3. Male gerbils were injected with adeno-associated virus (AAV) carrying shRNA targeting to Ezh2 into right dentate gyrus 2 weeks prior to forebrain ischemia. One week after ischemia, animals were injected with thymidine analogue to label proliferating cells. Three weeks after ischemia, animals were killed for histological analysis. AAV-mediated knockdown of Ezh2 significantly decreased the ischemia-induced increment of proliferating cells, and the proliferated cells after ischemia showed significantly longer migration from subgranular zone (SGZ), compared to the control group. Furthermore, the number of neural stem cells in SGZ significantly decreased after ischemia with Ezh2 knockdown group. Of note, Ezh2 knockdown did not affect the number of proliferating cells or the migration from SGZ in the non-ischemic condition. Our data showed that, specifically after ischemia, Ezh2 knockdown shifted the balance between self-renewal and differentiation toward differentiation in adult dentate gyrus.
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Human Gene Therapy 2024年2月22日 査読有り責任著者
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The Journal of Gene Medicine e3560 2023年6月30日 査読有り責任著者BACKGROUND: Fabry disease (FD) is an inherited lysosomal storage disease caused by deficiency of α-galactosidase A (α-Gal A) encoded by the GLA gene. The symptoms of FD occur as a result of the accumulation of globotriaosylceramide (Gb3), comprising a substrate of α-Gal A, in the organs. Adeno-associated virus (AAV)-mediated gene therapy is a promising treatment for FD. METHODS: α-Gal A knockout (GLAko) mice were injected intravenously with AAV2 (1 × 1011 viral genomes [vg]) or AAV9 (1 × 1011 or 2 × 1012 vg) vectors carrying human GLA (AAV-hGLA), and plasma, brain, heart, liver and kidney were tested for α-Gal A activity. The vector genome copy numbers (VGCNs) and Gb3 content in each organ were also examined. RESULTS: The plasma α-Gal A enzymatic activity was three-fold higher in the AAV9 2 × 1012 vg group than wild-type (WT) controls, which was maintained for up to 8 weeks after injection. In the AAV9 2 × 1012 vg group, the level of α-Gal A expression was high in the heart and liver, intermediate in the kidney, and low in the brain. VGCNs in the all organs of the AAV9 2 × 1012 vg group significantly increased compared to the phosphate-buffered-saline (PBS) group. Although Gb3 in the heart, liver and kidney of the AAV9 2 × 1012 vg was reduced compared to PBS group and AAV2 group, and the amount of Gb3 in the brain was not reduced. CONCLUSIONS: Systemic injection of AAV9-hGLA resulted in α-Gal A expression and Gb3 reduction in the organs of GLAko mice. To expect a higher expression of α-Gal A in the brain, the injection dosage, administration route and the timing of injection should be reconsidered.
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iScience 106487-106487 2023年3月 査読有り
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Internal medicine (Tokyo, Japan) 2022年2月1日 査読有り筆頭著者責任著者A 72-year-old woman presented with gradually-worsening myalgia and muscle weakness of the proximal lower limbs as well as elevated serum creatine kinase level. Based on a clinicoseropathological examination including a muscle biopsy, she was diagnosed with anti-signal recognition particle (SRP) myopathy. Although the myopathy relapsed two times in two years under oral prednisolone and intravenous immunoglobulin therapy, the myopathy remained in remission for more than three years after resection of gastric cancer. Although the anti-SRP myopathy is not considered to be cancer-associated in general, we should note that some cases of anti-SRP myopathy may be ameliorated with appropriate cancer treatment.
共同研究・競争的資金等の研究課題
14-
日本学術振興会 科学研究費助成事業 2022年4月 - 2026年3月
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鈴木謙三記念医科学応用研究財団 令和6年度調査研究助成金 2024年4月 - 2025年3月
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AMED 革新的医療技術創出拠点プロジェクト(東大拠点)シーズA 2024年4月 - 2025年3月
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日本学術振興会 科学研究費助成事業 2020年4月 - 2024年3月
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AMED 革新的医療技術創出拠点プロジェクト(東大拠点)シーズA 2021年4月 - 2023年3月