総合医科学研究所 難病治療学

土田 邦博

ツチダ クニヒロ  (Kunihiro Tsuchida)

基本情報

所属
藤田医科大学 医科学研究センター・ 難病治療学 教授
学位
学士(医学)(1988年3月 京都大学)
博士(医学)(1992年3月 京都大学)

研究者番号
30281091
J-GLOBAL ID
200901025890179259
researchmap会員ID
0000107006

外部リンク

筋骨格系疾患、糖尿病・肥満、神経変性疾患等の治療の難しい疾患の病態解明と治療法開発に関する研究を行っています。 モデル動物、ノンコーディングRNAの解析、RNA-seqやプロテオミクス等の網羅的解析、微量細胞の分取と分化培養,エクソソームを中心としたナノテクノロジーの医学応用等の先端技術を駆使して難病の病態生理の解明と治療法の基盤確立を目指した研究に取り組んでいます。


学歴

 2

論文

 170
  • Pwint Phoo Wai, Hisateru Yamaguchi, Keisuke Hitachi, Kunihiro Tsuchida, Setsuko Komatsu
    Oxygen 5(2) 4-4 2025年4月18日  査読有り
    Because soybean is sensitive to salt stress, it is necessary to improve their stress tolerance. Titanium-oxide nanoparticles (TiO2 NPs) enhanced the growth of soybean under salt stress. To elucidate the promotive effects of TiO2 NPs on soybean growth under salt stress, a gel-free/label-free proteomic analysis was carried out. The principal component analysis of proteins showed that TiO2 NPs affected proteins in roots grown under salt stress. The differentially changed proteins were associated with protein metabolism and transport in the biological process, the nucleus in the cellular component, and nucleic acid binding activity in the molecular function. Proteins identified with proteomics were verified using immunoblot analysis. The abundance of V-ATPase decreased in soybean under salt stress and increased with additional TiO2 NPs under stress, whereas xyloglucan endotransglucosylase/hydrolase did not change with any treatment. The abundance of peroxiredoxin increased under salt stress but decreased with additional TiO2 NPs under stress. These results suggest that TiO2 NPs confer salt tolerance in soybean plants at the early growth stage by regulating vacuole transport and reactive oxygen scavenging systems.
  • Setsuko Komatsu, Haruka Misaki, Wei Zhu, Hisateru Yamaguchi, Keisuke Hitachi, Kunihiro Tsuchida, Atsushi Higashitani
    Cells 14(7) 2025年4月3日  
    The role of a simulated microgravity environment on soybean growth was investigated. The root grew more under simulated microgravity conditions than in the presence of gravity. However, root shortening due to salt stress did not occur in simulated microgravity conditions. To reveal these mechanisms by simulated microgravity environment on soybean root, a proteomic analysis was conducted. Proteomic analysis revealed that among 1547 proteins, the abundances of proteins related to phytohormone, oxidative stress, ubiquitin/proteasome system, cell organization, and cell wall organization were altered under stimulated microgravity compared with gravity. Membrane-localized proteins and redox-related proteins were inversely correlated in protein numbers due to salt stress under gravity and the simulated microgravity condition. Proteins identified by proteomics were validated for protein accumulation by immunoblot analysis. Superoxide dismutase and ascorbate peroxidases, which are reactive oxygen species-scavenging proteins, increased in soybean root under salt stress but not in the simulated microgravity conditions even under stress. The accumulation of 45 kDa aquaporin and 70 kDa calnexin in soybean root under salt stress were increased in the simulated microgravity conditions compared to gravity. These findings suggest that soybean growth under salt stress may be regulated through improved water permeability, mitigation of reactive oxygen species production, and restoration of protein folding under simulated microgravity conditions.
  • Keisuke Hitachi, Hisateru Yamaguchi, Kunihiro Tsuchida
    Journal of Proteome Data and Methods 7 2 2025年4月  査読有り最終著者責任著者
  • Natsumi Ageta-Ishihara, Yugo Fukazawa, Fumiko Arima-Yoshida, Hiroyuki Okuno, Yuichiro Ishii, Keizo Takao, Kohtarou Konno, Kazuto Fujishima, Hiroshi Ageta, Hiroyuki Hioki, Kunihiro Tsuchida, Yoshikatsu Sato, Mineko Kengaku, Masahiko Watanabe, Ayako M Watabe, Toshiya Manabe, Tsuyoshi Miyakawa, Kaoru Inokuchi, Haruhiko Bito, Makoto Kinoshita
    Cell reports 44(3) 115352-115352 2025年2月27日  
    Transient memories are converted to persistent memories at the synapse and circuit/systems levels. The synapse-level consolidation parallels electrophysiological transition from early- to late-phase long-term potentiation of synaptic transmission (E-/L-LTP). While glutamate signaling upregulations coupled with dendritic spine enlargement are common underpinnings of E-LTP and L-LTP, synaptic mechanisms conferring persistence on L-LTP remain unclear. Here, we show that L-LTP induced at the perforant path-hippocampal dentate gyrus (DG) synapses accompanies cytoskeletal remodeling that involves actin and the septin subunit SEPT3. L-LTP in DG neurons causes fast spine enlargement, followed by SEPT3-dependent smooth endoplasmic reticulum (sER) extension into enlarged spines. Spines containing sER show greater Ca2+ responses upon synaptic input and local synaptic activity. Consistently, Sept3 knockout in mice (Sept3-/-) impairs memory consolidation and causes a scarcity of sER-containing spines. These findings indicate a concept that sER extension into active spines serves as a synaptic basis of memory consolidation.
  • Setsuko Komatsu, Rachel Koh, Hisateru Yamaguchi, Keisuke Hitachi, Kunihiro Tsuchida
    International journal of molecular sciences 26(1) 2024年12月30日  
    Wheat is one of the most extensively grown crops in the world; however, its productivity is reduced due to salinity. This study focused on millimeter wave (MMW) irradiation to clarify the salt-stress tolerance mechanism in wheat. In the present study, wheat-root growth, which was suppressed to 77.6% of the control level under salt stress, was recovered to the control level by MMW irradiation. To reveal the salt-stress tolerance mechanism of MMW irradiation on wheat, a proteomic analysis was conducted. Proteins related to cell cycle, proliferation, and transport in biological processes, as well as proteins related to the nucleus, cytoskeleton, and cytoplasm within cellular components, were inversely correlated with the number of proteins. The results of the proteomic analysis were verified by immunoblot and other analyses. Among the proteins related to the scavenging reactive-oxygen species, superoxide dismutase and glutathione reductase accumulated under salt stress and further increased in the MMW-irradiated wheat. Among pathogen-related proteins, pathogenesis-related protein 1 and the Bowman-Birk proteinase inhibitor decreased under salt stress and recovered to the control level in the MMW-irradiated wheat. The present results indicate that MMW irradiation of wheat seeds improves plant-growth recovery from salt stress through regulating the reactive oxygen species-scavenging system and the pathogen-related proteins. These genes may contribute to the development of salt-stress-tolerant wheat through marker-assisted breeding and genome editing.

MISC

 192

書籍等出版物

 16

講演・口頭発表等

 119

担当経験のある科目(授業)

 11

Works(作品等)

 1

共同研究・競争的資金等の研究課題

 29

その他

 3
  • ① 筋萎縮抑制薬開発。 ② 多種類の筋萎縮誘導モデル、新規二分脊椎モデル。 ③ ヒト正常筋や動物由来の高品質・高純度の筋幹細胞、筋支持細胞の取得技術 その細胞を用いた薬剤探索(筋の脂肪化抑制、骨化抑制)の応用実績。 ④ 乳がん由来細胞を用いた、転移・接着性の分子機構解析(エクソソーム分泌、ホルモン感受性、接着分子制御など)。
  • 近隣の高等学校から依頼を受け、難病研究の説明や研究室の見学を行なっている。
  • 教育内容・方法の工夫 医学部生や医療系コメディカルの講義を一部担当。講義内容の理解の助けとし、毎年改訂している。オンライン講義・対面講義の両方に工夫をしている。 医学部の少人数制の生物学の英語テキストの抄読会を行っている。 リサーチマインドを持った医学部学生のSRP(ステューデントリサーチャープログラム)で受け入れと研究指導を行なっている。 医療科学部卒論生の研究指導、発表会に向けた助言を行っている。

教育内容・方法の工夫(授業評価等を含む)

 3
  • 件名
    病理学
    開始年月日
    2010/04/01
    概要
    毎年ファイルを改定し、理解度チェックを入れるなど工夫している。
  • 件名
    Human Biology
    開始年月日
    2013/04/01
    概要
    医学部2年生の少人数制の英語抄読。医学英語力と発表能力のコンピタンス向上に向け、毎年工夫を凝らしている。2020年度はWeb講義として行っており、それに即した教育法を実践している。
  • 件名
    医学修士
    開始年月日
    2020/04/01
    概要
    オンライン講義で、医学部以外の出身者が医学的知識をつけれるように、わかりやすい説明を心がけている。