Team Director
Wataru Kimura Ph.D.

Laboratory for Heart Regeneration

Location Kobe / Developmental Biology Buildings

E-mail wataru.kimura[at]riken.jp

Please replace [at] with @.

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.

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

Selected Publications

Xiao F, Nguyen N, Wang P, et al.
Adducin Regulates Sarcomere Disassembly During Cardiomyocyte Mitosis
Circulation 150(10), (2024) doi: 10.1161/CIRCULATIONAHA.122.059102

Saito Y, Sugiura Y, Sakaguchi A, et al.
Postnatal xanthine metabolism regulates cardiac regeneration in mammals
bioRxiv (2024) doi: 10.1101/2024.07.24.605040

Nishiyama C, Saito Y, Sakaguchi A, et al.
Prolonged Myocardial Regenerative Capacity in Neonatal Opossum.
Circulation 146(2), 125-139 (2022) doi: 10.1161/CIRCULATIONAHA.121.055269

Sakaguchi A, Kawasaki M, Saito Y, et al.
Benzyl isothiocyanate induces cardiomyocyte proliferation and heart regeneration
bioRxiv 146, (2022) doi: 10.1101/2021.09.08.459197

Sakaguchi A, Kimura W.
Metabolic regulation of cardiac regeneration: roles of hypoxia, energy homeostasis, and mitochondrial dynamics
Current Opinion in Genetics & Development 70, 54-60 (2021) doi: 10.1016/j.gde.2021.05.009

Saito Y, Kimura W.
Roles of phase separation for cellular redox maintenance
Frontiers in Genetics 12, 691946 (2021) doi: 10.3389/fgene.2021.691946

Sakaguchi A, Nishiyama C, Kimura W.
Cardiac Regeneration as an Environmental Adaptatio
Biochimica et Biophysica Acta - Molecular Cell Research 1867(4), 118623 (2020) doi: 10.1016/j.bbamcr.2019.118623

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