Shigekazu Nagata

Osaka University


Primary Section: 43, Immunology and Inflammation
Secondary Section: 41, Medical Genetics, Hematology, and Oncology
Membership Type: International Member (elected 2015)

Biosketch

Shigekazu Nagata is a Distinguished Professor and Specially Appointed Professor at WPI Immunology Frontier Research Center at Osaka University in Japan. Dr. Nagata is a Biochemist and/or Molecular Biologist recognized for his work on cytokines and signal transduction induced by the cytokines. He is known particularly for his studies on the death factor and its receptor that have delineated the signal transduction and physiological role of apoptosis. Dr. Nagata was born and grown up in Kanazawa-City, Japan. He graduated from the University of Tokyo, Tokyo, Japan with a degree in Science, and from the University of Tokyo in 1977 with a Ph.D. in Biochemistry. He was a postdoctoral fellow in the Institute of Molecular Biology I, University of Zürich, Switzerland, and came back to Tokyo in 1982. He was Head of the Molecular Biology Department of Osaka Bioscience Institute, Professor in Department of Genetics, Osaka University Medical School, and Professor in Department of Medical Chemistry. He took the current position in 2015. He has been president of the Japanese Biochemical Society and Japanese Molecular Society of Japan and is the President of the Human Frontier Science Program Organization. He is a member of the National Academy of Science.

Research Interests

Shigekazu Nagata's laboratory identified Fas ligand (FasL) and its receptor (Fas) and proposed that apoptosis can be triggered by a death factor. He showed that mouse mutations (lpr and gld) that cause lymphadenopathy with systemic lupus erythematosus-type autoimmune disease are loss-of-function mutations in Fas or FasL, respectively. He then showed that caspases are activated during Fas-mediated apoptosis, and identified the enzyme (DNase) that causes the DNA fragmentation. Apoptotic cells are rapidly cleared by phagocytes. By establishing an assay for the engulfment of apoptotic cells, Nagata showed that two molecules (MFG-E8 and Tim4) recognize phosphatidylserine (PtdSer) and promote the engulfment of dead cells. In healthy cells, PtdSer is localized at the inner leaflet of plasma membranes and exposed to the cell surface when cells undergo apoptosis. He showed that two P4-type ATPases (ATP11A and 11C) translocate PtdSer from the outer to inner leaflet to maintain its asymmetrical distribution. During apoptosis, these ATPases are inactivated by caspases, while another protein called Xkr8 is activated by caspase to scramble phospholipids between the leaflets. Nagata proposes that PtdSer thus irreversibly exposed to the cell surface serves as an "eat me" signal.

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