Laboratory for Heart Regeneration | RIKEN BDR

Laboratory for Heart Regeneration

Team Leader

Wataru KimuraPh.D.

  • Location:Kobe / Developmental Biology Buildings
  • E-mail:wataru.kimura[at]riken.jpPlease replace [at] with @.
  • Lab Website

Research Summary

Heart disease is the leading cause of death worldwide. The main reason for this is our inability to regenerate damaged myocardium in the heart. Proliferation of cardiomyocytes (heart muscle cells), is a major mediator of mammalian heart regeneration in neonates and myocardial turnover in adults. However, little is known about the mechanisms regulating the cardiomyocyte cell cycle. We have recently shown that a rapid increase in mitochondrial respiration and in oxidative stress induce cell cycle arrest in neonatal cardiomyocytes. Our research interest focuses on how the postnatal mammalian heart loses regenerative capacity following 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 hypoxia signaling and oxidative stress in cardiomyocyte cell cycle regulation throughout the life cycle of mammals.

An M-phase marker pH3Ser10-positive cardiomyocyte in postnatal day 3 heart

Proliferative cardiomyocytes forming a cluster in the adult heart

Accumulation of oxidative DNA modification (8OHG) in adult cardiomyocytes

Research Theme

  • Dynamic change in kinetics of postnatal cardiomyocyte renewal
  • Role of hypoxia signaling in cardiomyocyte renewal
  • Induction of myocardial regeneration by engineering oxidative metabolism

Main Publications List

  • Nakada Y, Canseco D C, Thet S, et al.
    Hypoxia induces heart regeneration in adult mice.
    Nature 541. 222–227 (2017) doi :10.1038/nature20173
  • Kimura W, Xiao F, Canseco D C, et al.
    Hypoxia fate mapping identifies cycling cardiomyocytes in the adult heart.
    Nature 523. 226–230 (2015) doi:10.1038/nature14582
  • Canseco D C, Kimura W, Garg S, et al.
    Human ventricular unloading induces cardiomyocyte proliferation.
    Journal of the American College of Cardiology 65. 892–900 (2015) doi:10.1016/j.jacc.2014.12.027
  • Puente B N, Kimura W, Muralidhar S A, et al.
    The oxygen rich postnatal environment induces cardiomyocyte cell cycle arrest through DNA damage response.
    Cell 157. 565–579 (2014) doi: 10.1016/j.cell.2014.03.032

Member

Wataru KimuraTeam Leader wataru.kimura[at]riken.jp
Akane SakaguchiResearch Scientist akane.sakaguchi[at]riken.jp
Chihiro NishiyamaTechnical Staff I chihiro.nishiyama[at]riken.jp
Miwa KawasakiTechnical Staff I miwa.kawasaki[at]riken.jp

*:concurrent / Please replace [at] with @.