Research

Integrated functional analyses of disease-associated sugar chains lead to the establishment of glyco-medicine

The Project Leader's Profile

Eiji Miyoshi

1986, MD, Osaka University Medical School; 1986-90 Medical Training in Gastroenterology; 1994 PhD, Osaka University Graduate School of Medicine; 1995-99, Research Fellow; 2000, Assistant Professor, Dept. of Biochemistry, Osaka University Graduate School of Medicine; 2002, Associate Professor, Osaka University School of Medicine Allied Health Science; 2004-07, Associate Professor, Osaka University Graduate School of Medicine; 2007, Professor, Dept. of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine
Awards: Yamamura Prize in 1994; Young Investigator Awards of JACR in 2000 Windows フォト ギャラリー壁紙.jpg

Project Leader
  • Eiji Miyoshi (MD, PhD): Osaka University Graduate School of Medicine
    Department of Molecular Biochemistry and Clinical Investigation
Research Members
  • Shin-ichiro Shinzaki (Assistant Professor of Dept. of Molecular Biochemistry & Clinical Investigation)
  • Mika Terao (Research Fellow of Dept. of Dermatology)
Research Collaborators
  • Kenta Moriwaki  (NEDO Research Fellow)
  • Tomoko Yoshioka (Technical Assistant)
  • Naofumi Uozumi (Research Fellow)
  • ...., M.D., Ph.D., Professor, .... Osaka University Medical School/ Graduate School of Medicine

Summary

Our previous research was to focus on the biological functions of glycosyltransferases involved in the branching formation of N-glycans.  The project leader succeeded in the purification and cDNA cloning of several glycosyltransferases and analyzed their biological functions with sugar-remodeling systems.  Based on these data, we have started new glyco-projects, which are associated with diagnosis or therapy for cancer and gastroenterological diseases.  Tumor markers are not only monitors for diagnosis or therapy, but also represent the biological characters of cancer cells.  Therefore, it would lead the establishment of a novel therapy to analyze mechanisms underlying the production of tumor markers. To analyze the biological functions of sugar chains in details, we should evaluate the importance of a donor substrate for glycosyltransferases and the intracellular localization of sugar chains.  This concept is associated with an organelle network.  While a glycomic study is complicated, we should make a simple idea to apply it to the glyco-medicine.  The final goal of our study is to develop a therapeutic glycobiology for cancer and gastroenterogical diseases.       

Research projects

  1. Development of diseases markers for cancer and gastroenterogical diseases, using glyco-technology.
  2. Glycobiology for gastroenterology
  3. Glycobiology for cancer reserch
  4. Application of glyco-technology to health science

miyoshi_e.jpg Aberrant oligosaccharides are observed during carcinogenesis and have been used as tumor markers. Mutation or aberrant expression of glyco-genes, and/or the destruction of sorting system for glycoproteins cause the appearance of aberrant oligosaccharides in sera of patients with cancer. The detailed analyses of the mechanisms would lead to the establishment of novel bio-markers and therapy.

Some of Recent Papers

1. Nakagawa T, Uozumi N, Nakano M, Mizuno-Horikawa Y, Okuyama N, Taguchi T, Gu J, Kondo A, Taniguchi N, Miyoshi E.  (2006) Fucosylation of N-glycans regulates secretion of hepatic glycoproteins into bile ducts.  J. Biol. Chem. 281(40), 29797-29806.

2. Moriwaki K, Noda K, Nakagawa T, Asahi M, Yoshihara H, Taniguchi N, Hayashi N, Miyoshi E.  (2007) A high expression of GDP-fucose transporter in hepatocellular carcinoma is a key factor for increases in fucosylation.  Glycobiology 17(12), 1311-20.

3. Shinzaki S, Iijima H, Nakagawa T, Egawa S, Nakajima S, Ishii S, Irie T, Kakiuchi Y, Nishida T, Yasumaru M, Kanto T, Tsujii M, Tsuji S, Mizushima T, Yoshihara H, Kondo A, Miyoshi E, Hayashi N.  (2008) IgG oligosaccharide alterations are novel diagnostic marker for disease activity and the clinical course of inflammatory bowel disease.  Am. J. Gastroenterology 103(5), 1173-1181.

4. Moriwaki K, Noda K, Furukawa Y, Oshima K, Uchiyama A, Nakagawa T, Taniguchi N, Daigo Y, Nakamura Y, Hayashi N, Miyoshi E.  (2009) Deficiency of GMD leads to escape from NK cell-mediated tumor surveillance through modulation of TRAIL signaling.  Gastroenterology 137, 188-198.

5. Deguchi T, Tanemura M, Miyoshi E, Nagan H, Machida T, Ohmura Y, Kobayashi S, Marubashi S, Eguchi H, Takeda Y, Ito T, Mori M, Doki Y, Sawa Y. (2010) IncreasedIncreased immunogenicity of tumor-associated antigen, MUC1, engineered to express α-gal epitopes: A novel approach to immunotherapy in pancreatic cancer.  Cancer Res. in press.