Molecular Pharmacology (Pharmacology)

Staff List

Summary of Activity

Our laboratory investigates how cardiomyocyte proliferation is regulated and how this knowledge can be used to promote heart regeneration. Most adult mammalian cardiomyocytes have a limited capacity to divide, whereas fetal and neonatal cardiomyocytes retain substantial proliferative potential. Our previous work identified mitochondrial oxidative metabolism and oxidative stress as important contributors to postnatal cardiomyocyte cell-cycle arrest. Using molecular and cellular approaches and mouse genetics, we study the mechanisms linking metabolism to cell-cycle regulation, including how a subset of cardiomyocytes retains proliferative capacity after birth. Our goal is to identify strategies to stimulate endogenous cardiac repair.

Research Subject

1. Molecular mechanisms of postnatal cardiomyocyte cell-cycle arrest.
2. Roles of mitochondrial oxidative metabolism, oxygen availability, and redox signaling in cardiomyocyte proliferation.
3. Mechanisms that allow a subset of cardiomyocytes to retain proliferative capacity after birth.
4. Metabolic and pharmacological approaches to promoting endogenous heart regeneration.

Outlook for Research

We aim to establish a mechanistic basis for restoring the regenerative potential of the mammalian heart. By identifying the metabolic and redox-dependent processes that restrict cardiomyocyte proliferation, we seek to define targets for interventions that stimulate cardiac repair. We will investigate whether manipulating these processes can promote cardiomyocyte proliferation while preserving cardiac function. These studies may provide a foundation for future regenerative approaches to myocardial injury and heart failure.

Outlook for Students After Graduation

Students will develop skills in experimental design, molecular and cellular biology, and the analysis of animal models relevant to cardiovascular research. They will also gain experience in interpreting data, critically evaluating scientific literature, and communicating research findings. This training is intended to prepare students for further study and research careers in academia, biomedical research institutes, and the pharmaceutical and biotechnology sectors.

Major Publications

1. Sakaguchi A et al. Benzyl isothiocyanate induces heart regeneration. iScience. 2025;28:112724. 10.1016/j.isci.2025.112724

2. Saito Y, et al. Redox-dependent purine degradation triggers postnatal loss of cardiac regeneration potential. Redox Biology. 2025;79:103442. 10.1016/j.redox.2024.103442

3. Nishiyama C, et al. Prolonged Myocardial Regenerative Capacity in Neonatal Opossum. Circulation. 2022;146:125-139. 10.1161/CIRCULATIONAHA.121.055269

4. Nakada Y, et al. Hypoxia induces heart regeneration in adult mice. Nature. 2017;541:222-227. 10.1038/nature20173

5. Kimura W, et al. Hypoxia fate mapping identifies cycling cardiomyocytes in the adult heart. Nature. 2015;523:226-230. 10.1038/nature14582

6. Puente BN, Kimura W, et al. The oxygen-rich postnatal environment induces cardiomyocyte cell-cycle arrest through DNA damage response. Cell. 2014;157:565-579. 10.1016/j.cell.2014.03.032