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 - Basic Medicine (Core Departments) - Molecular Medicine
Medical Chemistry
Science is a fun. We hope that members in our Department have a full of curiosity to science, work hard, and enjoy Science. Using various techniques of Biochemistry and Molecular Biology, we are trying to unveil the mystery in life. Our devotion to science would contribute to the understanding of human diseases. Following the tradition of our Department that had been created by Former Professors Torasaburo Araki, Osamu Hayaishi, Tasuku Honjo, and others, we wish to create a new wave in Medical Chemistry.

  Shigekazu Nagata, Ph.D.
Research and Education
In our laboratory, we are studying the molecular mechanism of cell death, and its physiological and pathological roles. We identify molecules that are involved in cell death, and characterize them using techniques of Biochemistry, Molecular Biology, and mouse Genetics. We identified Fas ligand, a cytokine, that induces apoptosis in cells, and showed that apoptosis is executed by caspases (proteases) and CAD (caspase-activated DNase). Inefficient apoptosis by lack of the Fas ligand or its receptor Fas causes lymphoproliferation, leading to autoimmune diseases. Whereas, the excessive apoptosis by Fas ligand causes tissue destruction such as hepatitis. Apoptotic dead cells are swiftly engulfed by macrophages and degraded in lysosomes. We identified proteins (MFG-E8 and Tim-4) that is involved in engulfment of apoptotic cells, and showed that if apoptotic cells are not efficiently engulfed, they undergo secondary necrosis, leading to SLE (systemic lupus erythematosus)-type autoimmune diseases. We also identified an enzyme (DNase II) that digests chromosomal DNA of apoptotic cells after macrophage engulf them. If macrophages cannot digest DNA, they are activated and produce various cytokines including IFNb(beta) and TNFa(alpha), causing severe anemia or chronic polyarthritis. Phospholipids on plasma membranes are asymmetrically distributed between inner and outer leaflets. When cells undergo apoptosis, or platelets are activated, this asymmetrical distribution is disrupted, and phosphatidylserine exposed on the cell surface functions as an “eat me” signal, or trigger the blood clotting. We recently identified an enzyme (scramblase) that causes the exposure of phosphatidylserine on the activated platelets.

Medical Chemistry
Professor Shigekazu Nagata

Jun Suzuki,
Katsumori Segawa,
Hiroshi Yamaguchi,
Toshihiro Fujii
TEL +81-75-753-9441,
FAX +81-75-753-9446
MFG-E8-/- mice(-/-) show the enlarged and activated germinal centers (PNA-positive area), produce auto-antibodies, and develop SLE-type autoimmune disease.
DNase II-/- mice develop chronic polyarthritis.
The structure of TMEM16F that catalyzes scrambling of phospholipids on the plasma membranes
Members of the Department.
Recent Publications
1. Kawane, K., Ohtani, M., Miwa, K., Kizawa, T., Kanbara, Y., Yoshioka, Y., Yoshikawa, Y. and Nagata, S.: Chronic polyarthritis caused by mammalian DNA that escapes from degradation in macrophages. Nature 443: 998-1002, 2006.
2. Miyanishi, M., Tada, K., Koike, M., Uchiyama, Y., Kitamura, T. and Nagata, S.: Identification of Tim-4 as a phosphatidylserine receptor. Nature 450: 435-439, 2007.
3. Okabe, Y., Sano, T. and Nagata, S.: Regulation of the innate immune response by threonine phosphatase of Eyes absent. Nature 460: 520-524, 2009.
4. Suzuki, J., Umeda, M., Sims, P. J., and Nagata, S.: Calcium-dependent phospholipid scrambling by TMEM16F. Nature 468: 834-838, 2010.
5. Segawa, K., Suzuki, J. and Nagata, S.: Constitutive exposure of phosphatidylserine on viable cells. Proc. Natl. Acad. Sci. USA, 108: 19246-19251, 2011.