Shigekazu Nagata

Osaka University


Election Year: 2015
Primary Section: 43, Immunology and Inflammation
Secondary Section: 41, Medical Genetics, Hematology, and Oncology
Membership Type: Foreign Associate

Biosketch

Shigekazu Nagata is a biochemist recognized for his work on apoptosis. He is known particularly for his studies on Fas death factor that elucidated the physiological and pathological role of Fas-mediated apoptosis, and its signal transduction. Nagata was born in Kanazawa City, Ishikawa Prefecture, Japan, in 1949 and was grown up there. He graduated in 1972 from Tokyo University Faculty of Science with a Bachelor Degree in Biochemistry, and obtained PhD in Biochemistry in 1977 from Tokyo University Graduate School of Science. From 1977 to 1981, Nagata was a post-doctoral fellow in the Institute of Molecular Biology I, University of Zürich, Switzerland. In 1982, he returned to Japan as an assistant professor at the Institute of Medical Science, University of Tokyo. He was a head of Molecular Biology Department of Osaka Bioscience Institute from 1987 to1995, a professor in Department of Genetics, Osaka University Medical School from 1995 to 2007, and a professor in Department of Medical Chemistry, Kyoto University Graduate School of Medicine from 2007 to 2015. Nagata was a president of the Japanese Biochemical Society in 2005-2006, and the Japanese Society of Molecular Biology in 2007-2008. Nagata is a member of The Japan Academy, and a member of U.S. National Academy of Science.

Research Interests

Apoptosis is a term coined by Wyllie and his associates in 1972 to distinguish a morphologically distinct form of cell death. The molecular mechanism and physiological roles of apoptosis had been elusive for a long time due to few experimental systems to study this process. Nagata’s laboratory identified a receptor (Fas) and its ligand (Fas ligand) that mediate apoptotic cell death, and showed that loss-of function mutations of Fas and Fas ligand accelerate autoimmune diseases, accompanied by lymphoproliferation. The exaggeration of Fas-mediated apoptosis was shown to cause the tissue destruction. Nagata’s group then showed that when cells undergo apoptosis, a cascade of caspases is activated, and the caspases in the downstream of the cascade activate a specific DNase to cause DNA fragmentation. They also showed that the caspase-mediated cleavage inactivates a flippase responsible for maintaining the asymmetrical distribution of phospholipids at plasma membrane. While, caspase activates a scramblase that scrambles phospholipids at plasma membrane, thus exposing phosphatidylserine (PtdSer) to the cell surface. These features, the DNA fragmentation and PtdSer-exposure are major characteristics of apoptosis. Apoptotic cells are swiftly engulfed by macrophages to prevent the release of noxious materials from dead cells. Nagata’s group identified factors expressed in macrophages that recognize PtdSer exposed on apoptotic cells, and promote the engulfment of apoptotic cells.

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