Updated on 2025/05/16

写真a

 
Ishiura Hiroyuki
 
Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Professor
Position
Professor
External link

Degree

  • PhD ( 2011.3   The University of Tokyo )

  • MD ( 2002.3   The University of Tokyo )

Research Interests

  • Next-generation sequencer

  • repeat expansion diseases

  • Neurogenetics

Research Areas

  • Life Science / Neurology  / Neurogenetics

Education

  • The University of Tokyo   大学院医学系研究科  

    2007.4 - 2011.3

      More details

    Notes: 博士(医学)

    researchmap

  • The University of Tokyo   医学部医学科  

    1996.4 - 2002.3

      More details

    Notes: 学士(医学)

    researchmap

Research History

  • Okayama University   Graduate School of Medicine, Dentistry and Pharmaceutical Sciences   Professor

    2022.11

      More details

  • The University of Tokyo   Department of Neurology   Associate Professor/Senior Lecturer

    2020.4 - 2022.10

      More details

    Country:Japan

    researchmap

  • The University of Tokyo Hospital   Department of Neurology   Assistant Professor

    2012.4 - 2020.3

      More details

  • Japan Society for Promotion of Science   Research Fellowships for Young Scientists

    2010.4 - 2012.3

      More details

  • International Medical Center of Japan   Department of Neurology   resident

    2006.4 - 2007.3

      More details

▼display all

Committee Memberships

  • Japanese Society of Neurological Therapeutics   Councilor  

    2023.11   

      More details

    Committee type:Academic society

    researchmap

  • The Japanese Society of Internal Medicine   Councilor  

    2023.4   

      More details

    Committee type:Other

    researchmap

  • 日本神経学会   代議員  

    2021.5   

      More details

    Committee type:Academic society

    researchmap

  • 日本人類遺伝学会   評議員  

    2019.11   

      More details

    Committee type:Academic society

    researchmap

  • 日本人類遺伝学会   臨床遺伝専門医  

       

      More details

    Committee type:Academic society

    researchmap

▼display all

 

Papers

  • RFC1-related disorder presenting recurrent syncope. Reviewed International journal

    Yoko Tsuboyama, Akiko Takahashi, Sawako Furukawa, Asem Almansour, Masashi Hamada, Akatsuki Kubota, Jun Shimizu, Makoto Kinoshita, Chisato Fujimoto, Jun Mitsui, Takashi Matsukawa, Hiroya Naruse, Hiroyuki Ishiura, Shoji Tsuji, Tatsushi Toda

    Journal of neurology   271 ( 7 )   4635 - 4638   2024.3

     More details

    Authorship:Corresponding author   Language:English  

    DOI: 10.1007/s00415-024-12231-5

    PubMed

    researchmap

  • SPTLC2 variants are associated with early-onset ALS and FTD due to aberrant sphingolipid synthesis. Reviewed International journal

    Hiroya Naruse, Hiroyuki Ishiura, Kayoko Esaki, Jun Mitsui, Wataru Satake, Peter Greimel, Nanoka Shingai, Yuka Machino, Yasumasa Kokubo, Hirotoshi Hamaguchi, Tetsuya Oda, Tomoko Ikkaku, Ichiro Yokota, Yuji Takahashi, Yuta Suzuki, Takashi Matsukawa, Jun Goto, Kishin Koh, Yoshihisa Takiyama, Shinichi Morishita, Takeo Yoshikawa, Shoji Tsuji, Tatsushi Toda

    Annals of clinical and translational neurology   11 ( 4 )   946 - 957   2024.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a devastating, incurable neurodegenerative disease. A subset of ALS patients manifests with early-onset and complex clinical phenotypes. We aimed to elucidate the genetic basis of these cases to enhance our understanding of disease etiology and facilitate the development of targeted therapies. METHODS: Our research commenced with an in-depth genetic and biochemical investigation of two specific families, each with a member diagnosed with early-onset ALS (onset age of <40 years). This involved whole-exome sequencing, trio analysis, protein structure analysis, and sphingolipid measurements. Subsequently, we expanded our analysis to 62 probands with early-onset ALS and further included 440 patients with adult-onset ALS and 1163 healthy controls to assess the prevalence of identified genetic variants. RESULTS: We identified heterozygous variants in the serine palmitoyltransferase long chain base subunit 2 (SPTLC2) gene in patients with early-onset ALS. These variants, located in a region closely adjacent to ORMDL3, bear similarities to SPTLC1 variants previously implicated in early-onset ALS. Patients with ALS carrying these SPTLC2 variants displayed elevated plasma ceramide levels, indicative of increased serine palmitoyltransferase (SPT) activity leading to sphingolipid overproduction. INTERPRETATION: Our study revealed novel SPTLC2 variants in patients with early-onset ALS exhibiting frontotemporal dementia. The combination of genetic evidence and the observed elevation in plasma ceramide levels establishes a crucial link between dysregulated sphingolipid metabolism and ALS pathogenesis. These findings expand our understanding of ALS's genetic diversity and highlight the distinct roles of gene defects within SPT subunits in its development.

    DOI: 10.1002/acn3.52013

    PubMed

    researchmap

  • Expanded clinical spectrum of oculopharyngodistal myopathy type 1 Reviewed

    Takahiro Shimizu, Hiroyuki Ishiura, Manato Hara, Shota Shibata, Atsushi Unuma, Akatsuki Kubota, Kaori Sakuishi, Kiyoharu Inoue, Jun Goto, Yuji Takahashi, Yuichiro Shirota, Masashi Hamada, Jun Shimizu, Shoji Tsuji, Tatsushi Toda

    Muscle & Nerve   2022.9

     More details

    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    DOI: 10.1002/mus.27717

    researchmap

  • Isolated Paravermal Hyperintensities in Neuronal Intranuclear Inclusion Disease. Reviewed International journal

    Ryo Tokimura, Meiko Hashimoto, Akihiko Mitsutake, Souichi Sakai, Fumio Suzuki, Keiko Sugasawa, Chisato Fujimoto, Hiroyuki Ishiura, Tatsushi Toda

    Neurology   98 ( 22 )   938 - 939   2022.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1212/WNL.0000000000200590

    PubMed

    researchmap

  • Clinicopathologic Features of Oculopharyngodistal Myopathy With LRP12 CGG Repeat Expansions Compared With Other Oculopharyngodistal Myopathy Subtypes. International journal

    Theerawat Kumutpongpanich, Masashi Ogasawara, Ayami Ozaki, Hiroyuki Ishiura, Shoji Tsuji, Narihiro Minami, Shinichiro Hayashi, Satoru Noguchi, Aritoshi Iida, Ichizo Nishino, Madoka Mori-Yoshimura, Yasushi Oya, Kenjiro Ono, Toshio Shimizu, Akihiro Kawata, Shun Shimohama, Keiko Toyooka, Kaoru Endo, Shuta Toru, Oga Sasaki, Kenji Isahaya, Masanori P Takahashi, Kazuo Iwasa, Jun-Ichi Kira, Tatsuya Yamamoto, Michi Kawamoto, Tadanori Hamano, Kazuma Sugie, Nobuyuki Eura, Tomo Shiota, Mizuho Koide, Kanako Sekiya, Hideaki Kishi, Takuto Hideyama, Shigeru Kawai, Satoshi Yanagimoto, Hiroyasu Sato, Hajime Arahata, Shigeo Murayama, Kayoko Saito, Hideo Hara, Takashi Kanda, Hiroshi Yaguchi, Noboru Imai, Yuichi Kawagashira, Mitsuru Sanada, Kazuki Obara, Misako Kaido, Minori Furuta, Takashi Kurashige, Wataru Hara, Daisuke Kuzume, Mamoru Yamamoto, Jun Tsugawa, Hitaru Kishida, Naoki Ishizuka, Kohei Morimoto, Yukio Tsuji, Atsuko Tsuneyama, Atsuhiro Matsuno, Ryo Sasaki, Daigo Tamakoshi, Erika Abe, Shinichiro Yamada, Akiyuki Uzawa

    JAMA neurology   78 ( 7 )   853 - 863   2021.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Importance: Repeat expansion of CGG in LRP12 has been identified as the causative variation of oculopharyngodistal myopathy (OPDM). However, to our knowledge, the clinicopathologic features of OPDM with CGG repeat expansion in LRP12 (hereafter referred to as OPDM_LRP12) remain unknown. Objective: To identify and characterize the clinicopathologic features of patients with OPDM_LRP12. Design, Setting, and Participants: This case series included 208 patients with a clinical or clinicopathologic diagnosis of oculopharyngeal muscular dystrophy (OPDM) from January 1, 1978, to December 31, 2020. Patients with GCN repeat expansions in PABPN1 were excluded from the study. Repeat expansions of CGG in LRP12 were screened by repeat primed polymerase chain reaction and/or Southern blot. Main Outcomes and Measures: Clinical information, muscle imaging data obtained by either computed tomography or magnetic resonance imaging, and muscle pathologic characteristics. Results: Sixty-five Japanese patients with OPDM (40 men [62%]; mean [SD] age at onset, 41.0 [10.1] years) from 59 families with CGG repeat expansions in LRP12 were identified. This represents the most common OPDM subtype among all patients in Japan with genetically diagnosed OPDM. The expansions ranged from 85 to 289 repeats. A negative correlation was observed between the repeat size and the age at onset (r2 = 0.188, P = .001). The most common initial symptoms were ptosis and muscle weakness, present in 24 patients (37%). Limb muscle weakness was predominantly distal in 53 of 64 patients (83%), but 2 of 64 patients (3%) had predominantly proximal muscle weakness. Ptosis was observed in 62 of 64 patients (97%), and dysphagia or dysarthria was observed in 63 of 64 patients (98%). A total of 21 of 64 patients (33%) had asymmetric muscle weakness. Aspiration pneumonia was seen in 11 of 64 patients (17%), and 5 of 64 patients (8%) required mechanical ventilation. Seven of 64 patients (11%) developed cardiac abnormalities, and 5 of 64 patients (8%) developed neurologic abnormalities. Asymmetric muscle involvement was detected on computed tomography scans in 6 of 27 patients (22%) and on magnetic resonance imaging scans in 4 of 15 patients (27%), with the soleus and the medial head of the gastrocnemius being the worst affected. All 42 muscle biopsy samples showed rimmed vacuoles. Intranuclear tubulofilamentous inclusions were observed in only 1 of 5 patients. Conclusions and Relevance: This study suggests that OPDM_LRP12 is the most frequent OPDM subtype in Japan and is characterized by oculopharyngeal weakness, distal myopathy that especially affects the soleus and gastrocnemius muscles, and rimmed vacuoles in muscle biopsy.

    DOI: 10.1001/jamaneurol.2021.1509

    PubMed

    researchmap

▼display all

MISC

  • Spearmint extract Neumentix promotes the phagocytosis of Aβ by microglia in APP23 mice

    胡欣冉, 山下徹, 石浦浩之, 森原隆太, 福井裕介, 卞宇てい

    日本脳血管・認知症学会総会プログラム・抄録集   14th   2024

  • Mislocalized TAR DNA-binding protein-43 in mice stroke model

    卞宇てい, 福井裕介, 森原隆太, 石浦浩之, 山下徹

    日本脳血管・認知症学会総会プログラム・抄録集   14th   2024

  • 当科で経験した遺伝性プリオン病症例の検討

    平佑貴, 柚木太淳, 中野由美子, 松岡千加, 小坂田陽介, 河野智仁, 武本麻美, 森原隆太, 山下徹, 石浦浩之

    日本神経学会学術大会プログラム・抄録集   65th   2024

  • 当院における髄液IL-6高値患者の検討

    柚木太淳, 河野智仁, 平佑貴, 小坂田陽介, 中野由美子, 武本麻美, 森原隆太, 山下徹, 石浦浩之

    日本神経学会学術大会プログラム・抄録集   65th   2024

  • TARDBP遺伝子変異を認めた家族性ALSの家系の3症例の臨床経過の検討

    河野智仁, 柚木太淳, 成瀬紘也, 中野由美子, 平佑貴, 松岡千加, 小坂田陽介, 野村恵美, 武本麻美, 森原隆太, 山下徹, 石浦浩之

    日本神経学会学術大会プログラム・抄録集   65th   2024

▼display all

Awards

  • 日本神経学会賞

    2021.5   日本神経学会   神経筋疾患における新規リピート伸長病の発見

     More details

  • Award

    2018.10   The Japan Society of Human Genetics   Genetic study on neurological diseases

    ISHIURA Hiroyuki

     More details

  • English Presentation Award

    2018.10   The Japan Epilepsy Society   Expansions of intronic TTTCA and TTTTA repeats in benign adult familial myoclonic epilepsy

    ISHIURA Hiroyuki

     More details

  • Travel Award

    2011.10   The Japan Society of Human Genetics   Massively parallel sequence analysis reveals the causative gene of posterior column ataxia with retinitis pigmentosa

    ISHIURA Hiroyuki

     More details

Research Projects

  • Research on neurodegenerative disorders

    Grant number:23H02823  2023.04 - 2027.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    石浦 浩之, 角元 利行

      More details

    Grant amount:\18460000 ( Direct expense: \14200000 、 Indirect expense:\4260000 )

    researchmap

  • comprehensive search for expanded repeats in neurodegenerative diseaess

    Grant number:22H02823  2022.04 - 2025.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    辻 省次, 池内 健, 田中 真生, 石浦 浩之

      More details

    Grant amount:\17160000 ( Direct expense: \13200000 、 Indirect expense:\3960000 )

    researchmap

  • comprehensive search for expanded repeats in neurodegenerative diseaess

    Grant number:23K24085  2022.04 - 2025.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    辻 省次, 池内 健, 田中 真生, 石浦 浩之, 三井 純

      More details

    Grant amount:\17160000 ( Direct expense: \13200000 、 Indirect expense:\3960000 )

    本研究では、封入体形成が病理学的特徴である神経変性疾患に着目して、非翻訳領域の伸長リピート配列を探索し、神経変性疾患の発症機構を解明することを目的とする。この考え方は、非翻訳領域のリピート伸長配列は、Repeat Associated Non-AUG translation (RAN translation) を引き起こし、異常なアミノ酸配列を有するタンパクへの翻訳が行われ、その結果、封入体を形成するという仮説に基づいている。リピート伸長配列の検出は、short read sequencerでは困難であることから、long read sequencer による全ゲノムシーケンス解析を実施し、3-6塩基の繰り返し配列に焦点を当てて、伸長リピート配列を検出する独自に開発したプログラムを用いて、伸長リピート配列をゲノム全域から検出し、神経変性疾患の発症に関連する伸長リピート配列の発見を進めた。解析対象として、発症年齢の早いextreme phenotype を示すアルツハイマー病、家族歴を有する家族性アルツハイマー病症例を中心に7例を選択して、long read sequencer (Pacific Bioscience s 社のSequel II) を用いて、ロングリードシーケンス解析を実施した。long read sequencerは、error readを生じやすく精度が十分でないことから、circular consensus sequencing (CCS) というアルゴリズムにより、得られた全ゲノム配列データを用いた。その結果,これまでに報告のない、伸長リピート配列がさらに縦列に重複している例を見出した。本研究で開発したプログラムを用いて、伸長リピート配列の解析を進め、その疾患発症における意義の検討を進める。

    researchmap

  • Revealing pathogenesis of noncoding repeat expansion diseases using long-read sequencing

    Grant number:20H03588  2020.04 - 2023.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    石浦 浩之

      More details

    Grant amount:\17680000 ( Direct expense: \13600000 、 Indirect expense:\4080000 )

    ミオクローヌスてんかん患者でリピート伸長変異を有さない症例については全ゲノム配列解析を行い、通常のbasecallingに加えて、ExpansionHunterDenovoも使用してリピート配列のプロファイリングも行っている。これらの解析により、全ゲノム配列解析の有用性を含め、検討中である。
    ロングリード全ゲノム配列解析データについても現在データ解析中であるが、非常に高精度に塩基配列解析が出来ていることが判明している。特に、circular consensus sequencingにより実際高い精度を出せることがわかっている。
    伸長リピートを効率良く増幅することが可能になったため、ロングリードシーケンサーによる全長解読を行うために現在検体を準備している。また、PCR以外の方法を用いたリピート配列のクローニングも可能となり、この技術を用いて、機能解析に使用出来るコンストラクト作成を進めている。

    researchmap

  • Role of immune checkpoint molecules and macrophages in inflammatory myopathies

    Grant number:19K07956  2019.04 - 2022.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    SHIMIZU Jun

      More details

    Grant amount:\4030000 ( Direct expense: \3100000 、 Indirect expense:\930000 )

    The clinical and pathological features of myositis as a side effect of immune checkpoint inhibitors (irAE myositis) were analyzed in 12 cases to clarify the role of immune checkpoint molecules and macrophages. Similar pathology to irAE myositis was shown to be present in Graft-versus-host disease (GvHD) related myositis, revealing that immune checkpoint abnormalities are also involved in chronic GvHD myositis.In RNA-sequencing analysis of muscle samples from patients with inclusion body myositis (IBM) or polymyositis, it was revealed that, CDH1, which encodes the epidermal cell junction protein cadherin 1, was ectopically expressed in the muscles of IBM.

    researchmap

▼display all

 

Class subject in charge

  • Introduction to Medical Genomics (2024academic year) Second semester  - 木7~8

  • Neurology (Core Clinical Practice) (2024academic year) special  - その他

  • Practicals: Neurology (2024academic year) special  - その他

  • Research Projects: Neurology (2024academic year) special  - その他

  • Research Projects and Practicals: Neurology I (2024academic year) special  - その他

▼display all