Professor Hiroshi Nakada

Area and Subject Taught Immunochemistry
Research Theme(s) Cancer Cell Characteristics and Their Effect on Immune Mechanisms
Academic Degrees Doctor of Pharmacology, Kyoto University
Keywords for Research Field Tumor Immunology, Glycobiology, Mucin
Office Phone Number 81-75-705-1897
e-mail

Research Overview

Currently, one in every two to three Japanese dies of cancer. It is said that the 21st century will be the age of the life sciences, and one of the most expected advances is the discovery of a cure for cancer. Cancer cells are foreign matter within our bodies, and it is supposed to be the job of the body's immune defense to eliminate this kind of matter. However, cancer cells use clever methods to weaken our immune reactions or even to turn our immune systems against us, allowing themselves to multiply and spread. My research aims to elucidate, at the molecular level, the mechanism by which immunological competence is reduced, to develop methods to halt this process, and to apply these methods to new treatments for cancer. The most common cancer cells are derived from epithelial cells. This type of cell generates a glycoprotein called mucin, which is secreted into the cancerous tissue and blood of the patient. It is now becoming clear that this substance acts on the immune cells (monocytes/macrophages, B cells, NK cells, dendritic cells) via a variety of receptors, inhibiting their functioning. This research is one of central post-genome issues, and we anticipate that new advances can be made by combining it with research at the genetic level.

Notable Publications and Works in the Last Three Years

  1. S. Tanida, Y. Mori, A. Ishida, K. Akita, H. Nakada. Galectin-3 binds to MUC1-N-terminal domain and triggers recruitment of beta-catenin in MUC1-expressing mouse 3T3 cells. Biochim. Biophys. Acta. 1840: 1790-1797 (2014)
  2. K. Akita, M. Tanaka, S. Tanida, Y. Mori, M. Toda, H. Nakada. CA125/MUC16 interacts with Src family kinases, and over-expression of its C-terminal fragment in human epithelial cancer cells reduces cell-cell adhesion. Eur. J. Cell Biol. 92: 257-263 (2013)
  3. N. Zamri, N. Masuda, F. Oura, K. Kabayama, Y. Yajima, H. Nakada, K. Yamamoto, Y. Fujita-Yamaguchi. Characterization of anti-Tn-antigen MLS128 binding proteins involved in inhibiting the growth of human colorectal cancer cells. Biosci. Trends. 7: 221-229 (2013)
  4. S. Tanida, K. Akita, A. Ishida, Y. Mori, M. Toda, M. Inoue, M. Ohta, M. Yashiro, T. Sawada, K. Hirakawa, H. Nakada. Binding of the sialic acid binding lectin, Siglec-9, to the membrane mucin, MUC1, induces recruitment of beta-catenin and subsequent cell growth. J. Biol. Chem. 288: 31842-31852 (2013)
  5. Y. Matsumoto, Q. Zhang, K. Akita, H. Nakada, K. Hamamura, A. Tsuchida, T. Okajima, K. Furukawa, T. Urano. Trimeric Tn antigen on syndecan 1 produced by ppGalNAc-T13 enhances cancer metastasis via a complex formation with integrin alpha5beta1 and matrix metalloproteinase 9. J. Biol. Chem. 288: 24264-24276 (2013)
  6. H. Yurugi, S. Tanida, K. Akita, A. Ishida, M. Toda, H. Nakada. Prohibitins function as endogenous ligands for Siglec-9 and negatively regulate TCR signaling upon ligation. Biochem. Biophys. Res. Commun. 434: 376-381 (2013)
  7. H. Yurugi, S. Tanida, K. Akita, A. Ishida, M. Toda, and H. Nakada: Prohibitins function as endogenous ligands for Siglec-9 and negatively regulate TCR signaling upon ligation. Biochem. Biophys. Res. Commun. in press.
  8. H. Yurugi, S. Tanida, A. Ishida, K. Akita, M. Toda, M. Inoue, and H.Nakada: Expression of prohibitins on the surface of activated T cells. Biochem. Biophys. Res. Commun. 420: 275-280 (2012)
  9. K. Akita, S. Yoshida, Y. Ikehara, S. Shirakawa, M. Toda, M. Inoue, J.Kitawaki, H. Nakanishi, H. Narimatsu, and H. Nakada: Different levels of sialyl-Tn antigen expressed on MUC16 in endometriosis and ovarian cancer patients. Int. J. Gynecol. Cancer. 22: 531-538 (2012)
  10. N. Yuasa, H. Ogawa, T. Koizumi, K. Tsukamoto, A. Matsumoto-Takasaki, H. Asanuma, H. Nakada, and Y. Fujita-Yamaguchi. Construction and expression of anti-Tn-antigen-specific single chain antibody genes from hybridoma producing MLS128 monoclonal antibody. J. Biochem. 151: 371-381 (2012)
  11. Y. Matsumoto, Q. Zhang, K. Akita, H. Nakada, K. Hamamura, N. Tokuda, A. Tsuchida, T. Matsubara, T. Hori, T. Okajima, K.Furukawa, and T. Urano: pp-GalNAc-T13 induces high metastatic potential of murine Lewis lung cancer by generating trimeric Tn antigen. Biochem. Biophys. Res. Commun. 419: 7-13 (2012)
  12. A. Matsumoto-Takasaki, S. Hanashima, A. Aoki, N. Yuasa, H. Ogawa, R. Sato, H. Kawakami, M. Mizuno, H. Nakada, Y. Yamaguchi, and Y. Fujita-Yamaguchi: Surface plasmon resonance and NMR analyses of anti Tn-antigen MLS128 monoclonal antibody binding to two or three consecutive Tn-antigen clusters. J. Biochem. 151: 273-282 (2012)
  13. G. P. Subedi, T. Satoh, S. Hanashima, A. Ikeda, H. Nakada, R. Sato, M. Mizuno, N. Yuasa, Y. Fujita-Yamaguchi, and Y. Yamaguchi: Overproduction of anti-Tn antibody MLS128 single-chain Fv fragment in Escherichia coli cytoplasm using a novel pCold-PDI vector. Protein Expr. Purif. 82:197-204 (2012)
  14. A. Matsumoto-Takasaki, N. Yuasa, D. Katagiri, T. Koyama, K. Sakai, N. Zamri, S. Phung, S. Chen, H. Nakada, M. Nakata, and Y. Fujita-Yamaguchi: Characterization of three different single chain antibodies recognizing non-reducing terminal mannose residues expressed in Escherichia coli by an inducible T7 expression system. J. Biochem. 150:439-450 (2011)
  15. M. Hamaguchi, Y. Kawahito, H. Ishino, N. Takeuchi, D. Tokunaga, T. Hojo, A. Yamamoto, M. Kadoya, T. Seno, M. Kohno, and H. Nakada. Mucin from rheumatoid arthritis synovial fluid enhances interleukin-6 production by human peripheral blood ononuclear cells. Hum. Immunol. 72:241-248 (2011)