The 21st Century Center of Excellence Program

The Project Leader's Profile

Yoshihide Tsujimoto (Ph.D.)
Professor, Department of Medical Genetics, Osaka University Medical School/Graduate School of Medicine

In 1972, graduated from the Osaka University, School of Science. In 1977, completed the doctoral course at the Graduate School of Science, Osaka University and obtained his Ph.D. In 1977, Research Associate in Carnegie Institution, Dept. Embryology (Baltimore, USA). In 1979, appointed as Research Associate at National Institute for Basic Biology, Dept. Developmental Biology (Okazaki, Japan). In 1983, Associate Scientist at the Wistar Institute. In 1985, appointed as Assistant Professor at the Wistar Institute. In 1989, Associate Professor at the Wistar Institute. From 1991, he holds the current position. Specialized in molecular and cellular biology and biochemistry in cell death. He has received Leukemia Society of America Scholar (USA), Nissan Science Prize and Osaka Science Prize etc. He is also currently a research leader of SORST of Japan Science and Technology Agency.

Project Leader:	Yoshihide Tsujimoto, Ph.D., Professor, Department of Medical Genetics, Osaka University Medical School/Graduate School of Medicine
Research Members:	Yutaka Eguchi, Associate Professor, Department of Medical Genetics, Osaka University Medical School/Graduate School of Medicine Toshiharu Shibuya, Assistant professor, Department of Medical Genetics, Osaka University Medical School/Graduate School of Medicine Koei Shinzawa, Assistant Professor, Department of Medical Genetics, Osaka University Medical School/Graduate School of Medicine Toshiharu Shibuya, Assistant Professor, Department of Medical Genetics, Osaka University Medical School/Graduate School of Medicine
Research Collaborators:	Yosuke Matsuoka, Visiting Assistant Professor of the 21st Century COE from Feb.1, 2007, Department of Medical Genetics, Osaka University Medical School/Graduate School of Medicine Takashi Kodama, Post-Doctoral fellow of SORST of JST Zheng-Guo Cui, Post-Doctoral fellow of SORST of JST Others such as graduate students of Department of Medical Genetics, Osaka University Medical School/Graduate School of Medicine

Programmed cell death or apoptosis plays an integral role in a variety of biological events, including morphogenesis, tissue homeostasis, and removal of unwanted or harmful cells. Dysregulation of programmed cell death leads to various diseases in humans, including cancer and certain neurodegenerative diseases. The mitochondria play an essential role in the apoptotic death of mammalian cells by releasing various apoptogenic proteins, including cytochrome c, into the cytoplasm, which subsequently activates death-promoting proteolytic enzymes called caspases, that in turn cleave a set of cellular proteins and promote the death program. Mitochondrial dysfunction is also an important trigger for some forms of necrotic cell death. The Bcl-2 family of proteins regulates these mitochondrial changes during both apoptosis and necrotic cell death.
We are attempting to elucidate the molecular basis of apoptotic cell death as well as different forms of non-apoptotic programmed death, and aiming to develop some new strategies for treatment or prevention of a variety of human diseases which are caused by dysregulation of cell death.

1)	Nakagawa T, Shimizu S, Watanabe T, Yamaguchi O, Otsu K, Yamagata H, Inohara H, Kubo T, and Tsujimoto Y. The mitochondrial permeability transition dependent on Cyclophilin D regulates some forms of necrotic cell death, but not apoptotic cell death. Nature, 434, 652-658, 2005.
2)	Shigeomi S, Kanaseki T, Mizushima N, Mizuta K, Arakawa-Kobayashi S, Thompson CB, and Tsujimoto Y. A role of Bcl-2 family of proteins in non-apoptotic programmed cell death dependent on autophagy genes. Nature Cell Biol., 6, 1221-1228, 2004.
3)	Shinzawa K and Tsujimoto Y. PLA2 activity is required for nuclear shrinkage in caspase-independent cell death. J. Cell Biol., 163, 1219-1230, 2003.
4)	Konishi A, Shimizu S, Hirota J, Takao T, Fan Y, Matsuoka Y, Zhang L, Yoneda Y, Fujii Y, Skoultchi AI, and Tsujimoto Y. Involvement of histone H1.2 in apoptosis induced by DNA double-strand breaks. Cell, 114, 673-688, 2003.