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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.
Professor
Research and Education
In our laboratory, we identify molecules that are involved in growth, differentiation, and death of cells. We characterize the molecules using techniques of Biochemistry and Molecular Biology, and then analyze their physiological and pathological roles by establishing knock-out mice.
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 cells are swiftly recognized by macrophages and engulfed for digestion in lysosomes. We identified a protein (MFG-E8) 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 in mice. We also identified an enzyme (DNase II) that digests chromosomal DNA of apoptotic cells after macrophage engulf them. Inefficient digestion of DNA in macrophages induces anemia or chronic polyarthritis by IFNb(beta) or TNFa(alpha)that is produced by macrophages. G-CSF stimulates growth and differentiation of neutrophilic granulocytes. We identified G-CSF receptor, reconstituted the neutrophil differentiation system using the myeloid cell leukemia and cloned G-CSF receptor, and showed that STAT and C/EBP transcription factors play roles in the G-CSF-induced differentiation of neutrophils.


Molecular Medicine
Medical Chemistry
Professor ： Shigekazu Nagata
Associate
　Professor
：
Rikiro Fukunaga
Assistant
　Professor
：
Kohki Kawane,Rikinari Hanayama
TEL ： +81-75-753-9441,
+81-75-753-9445
FAX ： +81-75-753-9446
e-mail ： snagatamfour.med.kyoto-u.ac.jp
URL ： http://www2.mfour.med.kyoto-u.ac.jp/~nagata/
2. MFG-E8-/- mice produce anti-DNA Ab and anti-nuclear Ab, and develop SLE-type autoimmune disease.
3. On differentiation of red blood cells, nuclei extruded from reticulocytes expose phosphatidylserine that works an “eat nucleus” signal.
DNase II-/- mice develop chronic polyarthritis.
Members of the Department
Recent Publications
1. Hanayama, R., Tanaka, M., Miyasaka, K., Aozasa, K., Koike, M. Uchiyama, Y. & Nagata, S.: Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. Science. 304, 1147-1150, 2004.
2. Nagata, S.: DNA degrdation in development and programmed cell death. Annu. Rev. Immunol. 23: 853-75, 2005.
3. Yoshida, H., Kawane, K., Koike, M., Mori, Y., Uchiyama, Y. & Nagata, S.: Phosphatidylserine-dependent engulfment by macrophages of nuclei from erythroid precursor cells. Nature 437: 754-758, 2005.
4. 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.
5. 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.