Systems glycobiology and the role of glycans in disease

The Project Leader's Profile

Naoyuki Taniguchi

Endowed Chair Professor, Department of Disease Glycomics (SEIKAGAKU CORPORATION), the Institute of Scientific and Industirial Research (ISIR), Osaka University
Professor Emeritus, Osaka University
Group Director, System Glycobiology Research Group, Advanced Science Institute (ASI), RIKEN

Naoyuki Taniguchi graduated from the Hokkaido University School of Medicine, Sapporo , Japan in 1967 and obtained his MD degree and then his PhD at the same university in 1972. He was a visiting Associate Professor, Department of Biochemistry, Cornell Unviersity Medical College, New York and then became Associate Professor, Biochemistry Laboratory , Cancer Institute, Hokkaido University in 1977. He became a Professor and Chairman of the Department of Biochemistry, Osaka University Medical School from 1986-2006. He is now an Endowed Chair Professor of SEIKAGAKU CORPORATION, Department of Disease Glycomics, ISIR, Osaka University and Professor Emeritus. He is also serving as the Group leader for Systems Glycobilology Research Group, RIKEN ASI, and a member for Japanse Science Council. His research interest is mainly focused on the disease-related functional glycomics and redox regulation. He received Awards from Japan Medical Association, Takeda Foundation Award, International Glycoconjugate Organization Award, Medal with Purple Ribbon, IUBMB medal, HUPO Distinguished Service Award and so on. 

Project Leader
  • Professor: Naoyuki Taniguchi (MD., Ph.D.)
Research Members
  • Associate Professor: Kazuaki Ohtsubo (Ph.D.)
  • Assistant Professor: Congxiao Gao (M.D., Ph.D.)
  • Specially Appointed Assistant Professor: Kazuki Nakajima (Ph.D.)


We are conducting applied glycomics research to identify disease-associated glycans for the purpose of developing disease biomarkers and therapeutics. Prof. Taniguchi participates as a founding chair in HGPI (Human Disease Glycomics/Proteome Initiative), which is an initiative group in HUPO (Human Proteome Organization). HGPI has organized an international research project involving 21 institutes throughout the world that aims to normalize glycan analyses.

We have identified the glycosyltransferase genes that determine glycan structures. These include GnT-III, GnT-V, GnT-VI, GnT-IX, and Fut8. These genes are responsible for the branching on N-glycans (Asparagine-linked sugar-chains), which plays a critical role in determining glycan function. These observations have led to the novel strategy of "Sugar Remodeling", where the regulation of glycosyltransferase gene expression could be used to characterize novel functions of glycans.

Our major focus is to identify the target protein molecules of glycosyltransferases, as this will allow us to investigate the functions played by the glycosylation of the target protein. This would in turn improve our understanding of disease pathogenesis and the development of therapeutic tools. We are particularly interested in Fut8 (α1,6-fucosyltransfrerase), which adds core-fucose onto membrane proteins such as receptors. It has been shown that core-fucosylation of the target protein strictly determines the function of the receptor (e.g. Transforming Growth Factor β Receptor, TGFβ R) and alters the downstream cellular signaling cascade of the target protein.

Glycan Synthesis and Diseases   Glycosyltransferase genes have multiple functions in physiology and pathophysiology. We have revealed that core-fucosylation by Fut8 plays an important roll in physiology as a regulator of protein/enzyme function. The deletion of the Fut8 gene in mice causes severe growth retardation and early post-natal death. The surviving knockout mice show emphysema-like pathological changes in the lung. TGFβ R2 is a target protein of Fut8 and the core-fucose on this receptor is a factor that determines the receptor affinity for ligand. Without fucosylation on TGFβ R2, transforming growth factor (TGF) binds only loosely to the receptor, and this causes weaker signaling in the cell. This has further consequences, as it weakens the downstream phosphorylation of Smad2, which is needed to suppress the gene expression of matrix metalloproteinases (MMPs). Thus, weaker signaling due to the loss of core-fucosylation on TGFβ R2 induces the overexpression of MMPs, which leads to a higher degree of degradation of the extracellular matrix of the lung. Supporting this scenario is that the intraperitoneal injection of surviving Fut8 deletion mice with exogenous TGFβ1 significantly improved the emphysema-like changes and MMP expression in the lung. These data suggest there is a relationship between aberrant glycosylation due to a specific glycosyltransferase (Fut8) and the development of emphysema.

In order to understand systemically various functions of glycans and underlying mechanism of diseases due to glycan changes, we propose the new concept designated as "Glycan cycle" as a functional unit which consists of monosaccharides, nucleotide sugars, nucleotide transporters, glycosyltransferases, precursor for glycoproteins, matured glycoproteins and cell surface receptors such as EGFR, TGFR and Glut 2 etc.


Some of Recent Papers

  1. Taniguchi N. Nature Chem. Biology, 3, 307-309, 2007.
  2. Matsumura K, Higashida K, Ishida H, Hata Y, Yamamoto K, Shigeta M, Mizuno-Horikawa Y, Wang X, Miyoshi E, Gu J, Taniguchi N. Carbohydrate binding specificity of a fucose-specific lectin from Aspergillus oryzae: a novel probe for core fucose. J. Biol. Chem. 282, 15700-15708, 2007.
  3. Kotani N, Gu J, Isaji T, Udaka K, Taniguchi N, Honke K. Biochemical visualization of cell surface molecular clustering in living cells. Proc. Natl. Acad. Sci. U S A., 105, 7405-9740, 2007.
  4. Taniguchi N, Miyoshi E, Gu J, Honke K and Matsumoto A. Decoding sugar functions by identifying target glycoproteins. Curr. Opin. Struct. Biol., 16, 561-566, 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-β1 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.