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RIKEN Center for Biosystems Dynamics Research Laboratory for Heart Regeneration

Team Leader: Wataru Kimura (Ph.D.)

Research Summary

Wataru  Kimura(Ph.D.)

Heart disease is the number one killer of humankind mainly because the heart does not have regenerative capabilities. Our previous study indicated that oxidative stress is the main inducer of cell cycle arrest in postnatal mammalian heart muscle cells, cardiomyocytes. Our research interest is focused on why postnatal mammalian cardiomyocytes do not proliferate after injury- and age-related myocardial damage, and whether it is possible to re-awaken endogenous regenerative capacity. We utilize molecular and cellular tools and mouse genetics to understand the role of oxidative metabolism in cardiomyocyte cell cycle regulation throughout the life cycle of mammals.

Main Research Fields

  • Biology

Related Research Fields

  • Medicine, Dentistry & Pharmacy

Keywords

  • myocardial regeneration
  • oxidative stress
  • DNA damage
  • cell cycle

Selected Publications

Papers with an asterisk(*) are based on research conducted outside of RIKEN.

  • 1. Saito, Y., Sugiura, Y., Sakaguchi, A., Sada, T., Nishiyama, C., Maeda, R., Kaneko, M., Kiyonari,H. and Kimura, W.:
    "Postnatal xanthine metabolism regulates cardiac regeneration in mammals."
    bioRxiv 07.24.605040(2024)
  • 2. *Xiao, F., Nguyen, N., Wang, P., Li, S., Thet, S., Kimura, W., Luo, X., Lam, N., ElHelaly, W. Singh, R., Hsu, C., Ladha, F., Kanchwala, M., Hill, J., Menendez-Montes, I., Cardoso, A., Helena Pereira, A., Xing, C., Hajjar, R., Sadayappan, S., Hinson, J., and Sadek H. A.:
    "Adducin Regulates Sarcomere Disassembly During Cardiomyocyte Mitosis."
    Circulation Sep 3;150(10):791-805(2024)
  • 3. Kawakami, S., Yoshitane, H., Morimura, T., Kimura, W. and Fukada, Y.:
    "Diurnal shift of mouse activity by the deficiency of an ageing-related gene Lmna."
    J. Biochem.171, 509-518 (2022)
  • 4. Nishiyama C, Saito Y, Sakaguchi A, Kaneko M, Kiyonari H, Xu Y, Arima Y, Uosaki H, Kimura W.:
    "Prolonged Myocardial Regenerative Capacity in Neonatal Opossum"
    Circulation 146, 125-139 (2022)
  • 5. Iwasa, N., Matsui, T. K., Iguchi, N., Kinugawa, K., Morikawa, N., Sakaguchi, Y. M., Shiota, T., Kobashigawa, S., Nakanishi, M., Matsubayashi, M., Eura, N., Kiriyama, T., Izumi, T., Saito, K., Kataoka, H., Saito, Y., Kimura, W., Nishimura, Y., Mori, E., Sugie, K.:
    "Gene expression profiles of human cerebral organoids identify PPAR pathway and PKM2 as key markers for oxygen-glucose deprivation and reoxygenation."
    Front. Cell Neurosci. 15, 605030 (2021)
  • 6. Sakaguchi, A., Kawasaki, M., Saito, Y., Murata, K., Masumoto, H. and Kimura, W.:
    "Benzyl isothiocyanate induces cardiomyocyte proliferation and heart regeneration."
    bioRxiv 09.08.459197(2021)
  • 7. *Nakada, Y., Canseco, D. C., Thet S., Abdisalaam S., Asaithaymby A., Santos C. X., Shah A., Zhang, H., Faber, J. E., Kinter M. T., Szweda, L. I., Xing, C., Deberardinis, R., Oz O., Lu Z., Zhang C. C., #Kimura, W. and #Sadek, H. A.;
    "Hypoxia induces heart regeneration in adult mice"
    Nature 541, 222-227 (2017)
  • 8.*Kimura, W., Xiao, F., Canseco, D. C., Muralidhar, S., Thet S., Zhang, H. M., Abderrahman, Y., Chen, R., Garcia, J. A., Shelton, J. M., Richardson, J. A., Ashour, A. M., Asaithamby, A., Liang, H., Xing, C., Lu, Z., Zhang, C. C. and Sadek, H. A.:
    "Hypoxia fate mapping identifies cycling cardiomyocytes in the adult heart"
    Nature 523, 226-230 (2015)
  • 9. *Canseco, D. C., Kimura, W., Garg, S., Mukherjee, S., Bhattacharya, S., Abdisalaam, S., Das, S., Asaithamby. A., Mammen, P. P. and Sadek, H. A.:
    "Human ventricular unloading induces cardiomyocyte proliferation"
    J. Am. Coll. Cardiol. 65, 892-900 (2015)
  • 10. *Puente, B. N., *Kimura, W., Muralidhar, S. A., Moon, J., Amatruda, J. F., Phelps, K. L., Grinsfelder, D., Rothermel, B. A., Chen, R., Garcia, J. A., Santos, C. X., Thet, S., Mori, E., Kinter, M. T., Rindler, P. M., Zacchigna, S., Mukherjee, S., Chen, D. J., Mahmoud, A. I., Giacca, M., Rabinovitch, P. S., Aroumougame, A., Shah, A. M., Szweda, L. I. and Sadek, H. A.:
    "The oxygen rich postnatal environment induces cardiomyocyte cell cycle arrest through DNA damage response"
    Cell 157, 565-579 (2014)

Recent Research Results

Related Links

Lab Members

Principal investigator

Wataru Kimura
Team Leader

Core members

Yuichi Saito
Special Postdoctoral Researcher
Nobutoshi Ota
Research Scientist
Chihiro Nishiyama
Technical Staff I
Tai Sada
Junior Research Associate
Taketo Fukuhara
Student Trainee
Mingxuan Ju
Student Trainee

Contact Information

4F, RIKEN BDR Developmental Biology Bldg.A,
2-2-3 Minatojima-minamimachi, Chuo-ku
Kobe, Hyogo
650-0047 Japan
Email: wataru.kimura [at] riken.jp

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