Isao Matsuura, Ph.D.
Institute of Molecular and Genomic Medicine
Ph.D. Department of Chemistry, Faculty of Science, Hokkaido University (Japan) (1992)
B.S. Department of Chemistry, Faculty of Science, Hokkaido University (Japan) (1987)
1992-1995 Research Fellow, Department of Medical Biochemistry, Faculty of Medicine
University of Calgary (Canada)
1995-1997 Research Assistant, Department of Biochemistry, Hong Kong University of Science & Technology (Hong Kong)
1996-1997 Exchange Scholar, Department of Biochemistry & Molecular Biology, University of Melbourne (Australia)
1997-1999 Research Associate, Kresge Eye Institute, Wayne State University (USA)
1999-2003 Postdoctoral Fellow, Center for Advanced Biotechnology & Medicine, Rutgers University (USA)
2003-2006 Research Associate, Center for Advanced Biotechnology & Medicine, Rutgers University (USA)
2006-2014 Assistant Investigator, Division of Molecular Genomics & Medicine, National Health Research Institutes
2014-present Associate Investigator, Institute of Molecular Genomics & Medicine, National Health Research Institutes
Dr. Matsuura has been working on signal transduction studies for most of his career. His current research interests include transforming growth factor-b (TGF-b) and Interleukin-31 (IL-31) signalings in diseases. The former signaling pathways are involved in cancer development and metastasis, while the latter in an itchy skin disease called primary cutaneous amyloidosis (PCA) that is relatively common in Taiwan.
TGF-b signals propagate from cell surface to nucleus through cell the surface receptor and downstream effectors called Smads. Among the Smad proteins, the roles of Smad3 in cancer development and metastasis have drawn attention in recent years. Smad3 has several phosphorylation sites and its functions are modulated by the phosphorylation of those sites. The roles of some of those sites are well established, but the functional significance of some other sites is still not very clear. Using the recently-developed gene editing techniques, Dr. Matsuura and his laboratory members have generated mutant mice in which specific phosphorylation sites in Smad3 are substituted to non-phosphorylatable amino acid residues. Characterization of these mutations in breast cancer model mice is expected to provide important information regarding TGF-b-mediated breast cancer metastasis. Since cancer metastasis is the main cause of cancer patients’ death, this research is very important for novel therapeutic development in future.
IL-31 is a relatively new member of IL-family cytokine and its cell surface receptor is composed of two subunits, OSMRb and IL-31RA. Genetic analysis identified a link between misssense mutations in the either subunit and PCA. PCA is a relatively common skin disease in Taiwan and other South East Asian countries. It is characterized by deposition of amyloid on the lesional skin. The keratinocytes harboring the PCA mutation in the IL-31RA subunit secrete a much-reduced level of monocyte chemotactic protein-1 (MCP-1). Since MCP-1 is a chemokine that attracts inate immune cells that keep cellular debris from accumulating. Thus the reduction of MCP-1 may be a cause of the disease. Dr. Matsuura and the laboratory members have been searching for small molecules that can restore the MCP-1 level in the keratinocytes with the PCA mutations. They have identified multiple compounds that can partially restore the MCP-1 in the mutant cells. Since there is no direct treatment of the disease, this research may also provide useful information for novel therapy.
HIGHLIGHTS OF RECENT RESEARCH
Smad3 is a major intracellular effector in the TGF-b signal transduction. Its function is regulated by phosphorylation of multiple sites. Our laboratory found a proline isomerase Pin1 binds to Thr-179 of Smad3 when it is phosphorylated. This study demonstrated a novel link between two important players in cancer development (J Biol Chem (2010) 285, 1754).
The nonsense mutations of the large hepatitis B virus (HBV) lsurface (S) (LHBS) gene have been reported to have oncogenic potential. We showed the transforming growth factor induced (TGFBI) gene is silenced in the NIH3T3 cells transfected with a nonsense mutant of LHBS. Since TGFBI is a potential tumor suppressor, the silence of TGFBI may be a key event for the LHBS nonsense mutant-induced oncogenesis (BBA Mol Basis Dis (2014) 1842, 1080).
Primary cutaneous amyloidosis (PCA) is a relatively common itchy skin disorder in South America and Southeast Asia. Genetic analysis identified a link between missense mutations in the IL-31 receptor subunits and familial cases of PCA patients. We established a cultured cell-based disease model by introducing the PCA-derived mutation in the IL-31RA subunit of the IL-31 receptor. We found the mutation in the receptor subunit reduces the MCP-1 production. We suggested this phenomenon may be important for the development of the disease. (J Invest Dermatol (2013) 133, 1375)
HONORS & AWARDS
New Jersey Cancer Research Award for Scientific Excellence (2005)
- Chiu, S., Chung, H., Chen, Y., Huang, M., Huang, C., Huang, S., Matsuura, I*.A nonsense mutant of the hepatitis B virus large S protein antagonizes multiple tumor suppressor pathways through c-Jun activation domain-binding protein1. PLOS One Accepted(*corresponding author)
- Huang, C., Huang, M., Chung, H., Chiu, S., Yadav, P., Lin, Y., Liu, F., Matsuura, I*. Impaired mammary tumor formation and metastasis by the point mutation of a Smad3 linker phosphorylation site. BBA Mol. Basis Dis. (2018)1864, 3664-3671 (*corresponding author)
- Liu, F. Matsuura, I. Phosphorylation of Smads by intracellular kinases Methods in Molecular Biology, (2016) 1344, pp93-110
- Jiang, S. S., Huang, S. F., Huang, M. S., Chen Y. T., Jhong, H. J., Chang, I. C., Chen, Y. T., Chang, J. W., Chen, W. L., Lee, W. C., Chen, M. F., Yeh, C. T., Matsuura, I*. Dysregulation of the TGFBI gene is involved in the oncogenic activity of the nonsense mutation of hepatitis B virus surface gene sW182*. BBA Mol. Basis Dis. (2014)1842, 1080-1087 (*corresponding author)
- Chang, Y. T., Lin, C. H., Lee, C. T., Lin, M. W., Liu, L. Y., Chen, C. C., Lee, D. D., Liu, H. N., Tsai, S. F., Matsuura, I*. Detection of Common Mutations in Sporadic Primary Localized Cutaneous Amyloidosis by DNA Mass Spectrometry. Br. J. Dermatol. (2014) 170, 974-976. (*corresponding author)
- Shiao, YM., Chung, HJ., Chiang, KN., Chang, YT., Lee, DD., Chen CC., Lin, MW., Tsai, SF. and Matsuura, I*. MCP-1 as an effector of IL-31 signaling in familial primary cutaneous amyloidosis. J. Invest. Dermatol. (2013) 133, 1375-1378. (*corresponding author)
- Matsuura, I*., Lai, C. and Chiang, K. Functional interaction between Smad3 and S100A4 (Metastatin-1) for TGF-β-mediated cancer cell invasiveness. Biochem. J. (2010) 426, 327-35. (*corresponding author)
- Matsuura, I*., Chiang, K., Lai, C., He, D., Wang, G., Ramkumar,R., Uchida, T., Ryo, A., Lu, K. and Liu, F. Pin1 promotes TGF-β-induced migration and invasion. J. Biol. Chem. (2010) 285, 1754-64. (*corresponding author)