Integrated Functional analyses of disease-associated sugar chains and proteins The 21st Century Center or Excellence Program
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Studies on the therapeutic approach by using glyco-genes

The Project Leader's Profile
Akihiro Kondo (Ph.D.)
Visiting Professor, Department of Glycotherapeutics and Research Center for Systems Glycobiology, Osaka University Medical School/ Graduate School of Medicine

In 1980, graduated from Gifu University, Department of Agriculture. In 1982, obtained his M.S. at the Graduate School of Agriculture, Gifu University, and started to work at Central Research Laboratories, Takara Shuzo Co., Ltd. as a researcher. In 1986, Visiting Researcher at Department of Science, Osaka University. In 1992, Senior Scientist at Biotechnology Research Laboratories, Takara Shuzo Co., Ltd. In 1994, obtained his Ph.D. at the United Graduate School of Agricultural Sciences, Gifu University. In the same year, Visiting Researcher at Cytel Corporation in U. S.A. In 2002, Senior Researcher at DNA Function Analysis Center of Takara Bio Inc. From 2002, he holds the current position. Specialized in carbohydrate chemistry and analytical chemistry. Major works include ‘Oligosaccharide Analysis by Fluorescence Labeling’ and ‘Development of the Test Method for Detection of Endocrine Disrupting Activity Using DNA Microarrays’ in ‘Toxicogenomics’.
Project Leader:

Akihiro Kondo, Ph.D., Visiting Professor, Department of Glycotherapeutics and Research Center for Systems Glycobiology, Osaka University Medical School/ Graduate School of Medicine
Research Members:

Takatoshi Nakagawa, Assistant Professor, Department of Glycotherapeutics and Research Center for Systems Glycobiology, Osaka University Medical School/ Graduate School of Medicine

Research Collaborators: Wenzhe Li, Post-doctoral fellow of the 21st Century COE Program of Department of Glycotherapeutics and Research Center for Systems Glycobiology, Osaka University Medical School/ Graduate School of Medicine


Summary


Comprehensive analysis of Glyco-gene deficient mice Alpha 1,6-fucosyltransferase (FUT8) catalyzes the transfer of L-fucose to the innermost GlcNAc in N-linked sugar chain. FUT8 knock out (KO) mice showed severe phenotypes, such as growth retardation, semi-lethality, and emphysema. Microarray analysis revealed several genes tare dysregulated in this mutant mice. Trypsin is a representative gene and drastically downregulated. Downregulaton of trypsin was also found in FUT8 knock down (KD) cells with siRNA. PAR-2, a G-protein coupled receptor and activated by trypsin, has been shown to be involved in several biological processes including cell proliferation. We proposed down regulation of trypsin expression cause suppression of cell proliferation through inability to activate PAR-2 in FUT8 KD cells. To further gain insight into the relationship between trypsin and phenotypes of FUT8 KO mice, comprehensive approach has been taking from several aspects.
Functional of sugar chains and proteins

Some of Recent Papers


1) Kondo A, Li W, Nakagawa T, Nakano M, Koyama N, Wang X, Gu J, Miyoshi E, and Taniguchi N. From glycomics to functional glycomics of sugar chains: identification of target proteins with functional changes using gene targeting mice and knock down cells of FUT8 as examples. Biochim. Biophys. Acta., 1746, 1881-1889, 2006.
2) Zhao Y, Nakagawa T, Itoh S, Inamori KI, Isaji T, Kariya Y, Kondo A, Miyoshi E, Miyazaki K, Kawasaki N, Taniguchi N, and Gu J. N-acetylglucosaminyltransferase III antagonizes the efferct of N-acetylglucosaminyltransferase V on alpha 3beta 1 integrin-mediated cell migration. J. Biol. Chem., 281, 43, 32122-32130, 2006.
3) Nakagawa T, Uozumi N, Nakano M, Mizuno-Horikawa Y, Okuyama N, Taguchi T, Gu J, Kondo A, Taniguchi N, and Miyoshi E. Fucosylation of N-glycans regulates the secretion of hepatic glycoproteins into bile ducts. J. Biol. Chem., 281, 40, 29797-29806, 2006.
4) Li W, Nakagawa T, Koyama N, Wang X, Jin J, Mizuno-Horikawa Y, Gu J, Miyoshi E, Kato I, Honke K, Taniguchi N, and Kondo A. Down-regulation of trypsinogen expression is associated with growth retardation in {alpha}1,6-fucosyltransferase-deficient mice: attenuation of proteinase-activated receptor 2 activity. Glycobiology, 16, 1007-1019, 2006.
5) Wang X, Inoue S, Gu J, Miyoshi E, Noda K, Li W, Mizuno-Horikawa Y, Nakano M, Asahi M, Takahashi M, Uozumi N, Ihara S, Lee SH, Ikeda Y, Yamaguchi Y, Aze Y, Tomiyama Y, Fujii J, Suzuki K, Kondo A, Shapiro SD, Lopez-Otin C, Kuwaki T, Okabe M, Honke K, and Taniguchi N. Dysregulation of TGF-beta 1 receptor activation leads to abnormal lung development and emphysema-like phenotype in core fucose-deficient mice. Proc. Natl. Acad. Sci. USA., 102, 15791-15796, 2005.
 

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Integrated functional analyses of disease-associated sugar chains and proteins, Osaka University