Laboratory for Heart Regeneration
Location Kobe / Developmental Biology Buildings
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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.
- Dynamic change in kinetics of postnatal cardiomyocyte renewal
- Role of hypoxia signaling in cardiomyocyte renewal
- Induction of myocardial regeneration by engineering oxidative metabolism
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
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
Team LeaderWataru Kimura
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Research ScientistAkane Sakaguchi
Special Postdoctoral ResearcherYuichi Saito
Technical Staff IChihiro Nishiyama
Technical Staff IMiwa Kawasaki
Student TraineeTai Sada
Student TraineeTaketo Fukuhara
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