Curriculum Vitaes
  1. Researcher Search Results
  2. Keisuke Hitachi

Keisuke Hitachi

  (常陸 圭介)

Profile Information

Affiliation
Senior Assistant Professor, Center for Medical Science, Fujita Health University
Degree
Ph.D.(The University of Tokyo)
Contact information
hkeisukefujita-hu.ac.jp
Researcher number
10508469
ORCID ID
 https://orcid.org/0000-0002-7300-5238
J-GLOBAL ID
200901097490734327
researchmap Member ID
6000011163
External link

Muscle increases with training, decreases with disuse, and markedly changes its properties during aging and disease. Skeletal muscle is not only responsible for body movement but is also a highly plastic organ that contributes to whole-body metabolism and homeostasis. I aim to elucidate the molecular mechanisms that govern the adaptation and deterioration of skeletal muscle, with the goal of advancing our understanding of muscle dysfunction associated with aging and disease and ultimately contributing to its prevention and treatment.

My previous work has addressed the mechanism by which myostatin inhibition increases muscle mass and demonstrated that miR-486 is involved in part of this process. I also identified the long non-coding RNA Myoparr as a novel regulatory molecule involved in muscle atrophy and myogenic differentiation, and clarified the relationship between Myoparr-mediated transcriptional regulation and muscle formation and function. More recently, I have found that the simultaneous loss of multiple myosin heavy chains causes severe muscle atrophy.

Currently, I combine i-GONAD-based generation of genetically modified mice, skeletal muscle-directed AAV-mediated gene delivery, proteomics, and transcriptome analyses to investigate molecular mechanisms and to validate their functions in vivo in an integrated manner. Using these approaches, I am focusing on the physiological and pathological significance of post-translational modifications in skeletal muscle, particularly methylation, and analyzing their relationships with muscle function, fiber-type properties, and aging-related changes. Through these studies, I seek to uncover new molecular bases linking skeletal muscle adaptation and deterioration, and to build a foundation for intervention strategies against sarcopenia and muscle diseases.

Research Interests

 12

Research Areas

 3

Research History

 4

Committee Memberships

 5

Awards

 6
More

Papers

 73
  • Miyuka Suzuki, Takahito Ohshiro, Yuki Komoto, Keisuke Hitachi, Masateru Taniguchi
    Analytical sciences : the international journal of the Japan Society for Analytical Chemistry, 42(9) 817-825, Sep, 2026  
    Lysine methylation is an important epigenetic modification that regulates chromatin structure and gene expression. However, it is still difficult to distinguish its methylated states without labels at the single-molecule level. In this study, we investigate the discrimination of lysine methylation states using single-molecule tunneling measurements with gold nano-gap electrodes. The conductance decreases stepwise as the number of methyl groups increases, even though density functional theory (DFT) shows that all molecules have almost the same HOMO energy levels. This result suggests that conductance is not determined only by the electronic structure, but also by how the molecule is arranged between the electrodes. Statistical analysis of current signals shows that high-conductance events become less frequent after methylation, indicating fewer strongly coupled configurations. The relationship between current and molecular length also supports that transport depends on variations in molecular configurations. Machine learning analysis achieved an F-score of 0.76 for distinguishing methylated from unmethylated lysine. In contrast, distinguishing between mono-, di-, and trimethylated forms gave a lower F-score of 0.49, reflecting overlap in the signals. These results suggest that single-molecule tunneling currents are sensitive to stepwise lysine methylation states through differences in transient molecular configurations. This work demonstrates the potential of single-molecule tunneling measurements for label-free analysis of epigenetic modifications.
  • Setsuko Komatsu, Shafiq Ur Rehman, Hisateru Yamaguchi, Keisuke Hitachi, Kunihiro Tsuchida
    International journal of molecular sciences, 27(16), Aug 17, 2026  
    Salt stress severely limits wheat growth and seed yield; however, the mechanisms underlying plant-derived smoke (PDS)-induced salt tolerance remain unclear. The present study performs membrane proteomics to clarify how PDS solution enhances salt tolerance in wheat. Immunoblot analysis of subcellular marker proteins confirms successful enrichment of membrane fractions. Principal component analysis shows that 200 mM NaCl markedly alters membrane-protein composition in wheat roots, whereas 2000 ppm PDS solution largely restores these changes even under salt stress. At the protein level, mitochondrial ascorbate peroxidase increases in roots under salt stress but decreases with PDS-solution treatment, while leaves show the opposite trend. Salt stress reduces ATP content and H+-ATPase abundance; PDS-solution treatment restores both to near-control levels. In contrast, aquaporin levels increase under salt stress but decline after PDS-solution application. In addition, the expression of ammonium transporter was downregulated significantly under salt stress but recovered with PDS-solution treatment. These results suggest that PDS solution may confer salt-stress tolerance to wheat by regulating energy metabolism, water permeability, and ammonium absorption in the root membrane.
  • Sheikh Shohag, Hisateru Yamaguchi, Keisuke Hitachi, Kunihiro Tsuchida, Shafiq Ur Rehman, Setsuko Komatsu
    Proteomes, Jun 15, 2026  
  • Katsuya Morito, Natsuki Nishikawa, Keisuke Hitachi, Rina Tamaki, Minori Nishikawa, Yoshio Hayashi, Kunihiro Tsuchida, Kentaro Takayama
    ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE, May 26, 2026  
  • Keisuke Hitachi, Shunya Sadaki, Masato Watanabe, Ryosuke Tsuji, Atsushi Kubo, Yuki Yamasaki, Yuri Kiyofuji, Masafumi Inui, Takashi Kudo, Tomohiko Suzuki, Satoru Takahashi, Kunihiro Tsuchida, Ryo Fujita
    Apr 23, 2026  
    Inducing fast myofiber programs offers therapeutic potential for skeletal muscle disorders such as sarcopenia, where fast myofibers are preferentially lost. Engineered muscle-specific AAV (MyoAAV) vectors enable efficient transduction of skeletal muscles after systemic administration; however, cardiac transgene expression limits applications requiring skeletal muscle-selective delivery. We generated modified MyoAAV vectors by incorporating cardiac-specific miR-208a target sequences into the transgene 3′UTR. This design markedly suppressed cardiac expression while preserving skeletal muscle output, with target-site variation enabling tunable trade-offs between cardiac detargeting and skeletal muscle expression levels. We validated this platform using neural retina leucine zipper (Nrl), a large Maf transcription factor regulating type IIb myofiber identity. Systemic delivery of conventional MyoAAV-Nrl caused severe cardiac hypertrophy and uniform lethality within one month. Conversely, incorporating miR-208a target sequences prevented detectable hypertrophy and eliminated mortality during the experimental observation period. This modification significantly reduced cardiac Nrl expression while maintaining skeletal muscle levels, successfully promoting type IIb myofiber formation and hypertrophy across multiple skeletal muscles. These findings demonstrate that miR-208a-mediated cardiac detargeting combined with MyoAAV-Nrl enables safe systemic induction of fast myofiber remodeling and hypertrophy, establishing a platform for gene therapies targeting skeletal muscle disorders associated with fast myofiber loss.
More

Misc.

 1

Books and Other Publications

 4

Presentations

 90

Teaching Experience

 10
More

Professional Memberships

 2

Research Projects

 28
More

Industrial Property Rights

 1

Academic Activities

 8
More

Social Activities

 4

Media Coverage

 4

Other

 1

その他教育活動上特記すべき事項

 24
  • 件名（英語）
    2020年　アセンブリ2活動
    開始年月日（英語）
    2020/04/01
    終了年月日（英語）
    2020/11/30
  • 件名（英語）
    2020年度　医学部医学研究演習
    開始年月日（英語）
    2020/02/03
    終了年月日（英語）
    2021/02/26
  • 件名（英語）
    2019年　医療科学部卒業研究指導
    開始年月日（英語）
    2019/06/01
    終了年月日（英語）
    2019/10/20
  • 件名（英語）
    2018年　医療科学部卒業研究指導
    概要（英語）
    「ヒトMettl21e相同遺伝子が偽遺伝子に変化した要因の同定」
  • 件名（英語）
    藤田保健衛生大学医学部FD講演会
    概要（英語）
    「良い講義について ～殿堂入りした教員が教える講義の秘訣～」参加
  • 件名（英語）
    藤田保健衛生大学大学院保健学研究科FD研修講演会
    概要（英語）
    「鳥取大学医学部における産学連携教育"発明楽"による発想力育成教育の実践」に参加
  • 件名（英語）
    2018年　アセンブリ2活動
    概要（英語）
    サイエンスカフェ
  • 件名（英語）
    2017年　医療科学部卒業研究指導
    概要（英語）
    「定量的RT-PCRを用いた骨格筋の肥大・萎縮時における長鎖非コードRNAの発現変動 の解析」
  • 件名（英語）
    2017年　医療科学部卒業研究指導
    概要（英語）
    「骨格筋細胞を用いた筋量調節に関わる脱ユビキチン化酵素の探索」
  • 件名（英語）
    2017年　アセンブリ2活動
    概要（英語）
    サイエンスカフェ
  • 件名（英語）
    2016年　藤田保健衛生大学総医研・最先端医学研究セミナー・大学院医学研究科医学セミナー
    概要（英語）
    転写調節領域由来長鎖ノンコーディングRNAを介した遺伝子発現制御機構の解析
  • 件名（英語）
    2016年　アセンブリ1活動
    概要（英語）
    インターネットチュートリアル
  • 件名（英語）
    2016年　医療科学部卒業研究指導２名
    概要（英語）
    「骨格筋の肥大・萎縮における長鎖ノンコーディングRNAの発現探索」
  • 件名（英語）
    2016年　基礎医学体験実習指導２名
    概要（英語）
    実験の指導
  • 件名（英語）
    2015年　医療科学部卒業研究指導２名
    概要（英語）
    「医学応用を目指した骨格筋の肥大・萎縮制御に関わる有用分泌因子の探索」
  • 件名（英語）
    2015年　アセンブリ1活動
    概要（英語）
    インターネットチュートリアル
  • 件名（英語）
    藤田保健衛生大学医療科学部第２回FD講演会
    終了年月日（英語）
    2015/06/02
    概要（英語）
    「高大連結の状況について」に参加
  • 件名（英語）
    2014年　サマースチューデント指導
    概要（英語）
    医学部大学院生の研究指導
  • 件名（英語）
    2014年　基礎医学体験実習指導
    概要（英語）
    実験の指導
  • 件名（英語）
    2014年　藤田保健衛生大学大学院医学研究科・医学セミナー
    概要（英語）
    骨格筋細胞の分化における長鎖非コードRNAによる転写調節機構の解析
To the list screen