Micro-signaling Regulation Technology Unit

We make basic and applied studies on drug discovery against HBV through development of a unique detection technique(s) and high throughput screenings on novel micro-signaling (therapeutic) targets, discovered using clinical samples from patients with virus infection, liver fibrosis/cirrhosis, liver degeneration, hepatic cancer, and cancer angiogenesis.

Research Fields

Chemistry / Biology & Biochemistry / Molecular Biology & Genetics / Pharmacology & Toxicology / Clinical Medicine

Research Subjects

• Detection/regulation of hepatic fibrosis targeting TGF-β activation reaction
• Drug discovery for HBV utilizing multiple next-generation life science technologies
• Studies on screening compounds that selectively suppress pathogenesis

Publications

1. Kuo, TF., Tatsukawa, H., and Kojima, S.:
   "New insights into functions and localization of nuclear transglutaminase 2."
   FEBS J. 278(24), 4756-4767 (2012)
2. Kuo, TF., Tatsukawa, H., and Kojima, S.:
   "Regulation of transglutaminase-mediated hepatic cell death in alcoholic steatohepatitis and non-alcoholic steatohepatitis."
   J. Gastro. Hepatol. 27(suppl 2), 52-57 (2012).
3. Kuo, TF., Tatsukawa, H., Matsuura, T., Nagatsuma, K., Hirose, S., and Kojima, S.:
   "Free fatty acids induce transglutaminase 2-dependent apoptosis in hepatocytes via ER stress-stimulated PERK pathways."
   J Cell Physiol. 227, 1130-1137 (2012).
4. Tatsukawa, H., Sano, T., Fukaya, Y., Ishibashi, N., Watanabe, M., Okuno, M., Moriwaki, H., and Kojima, S.:
   "Dual induction of caspase 3- and transglutaminase-dependent apoptosis by acyclic retinoid in hepatocellular carcinoma cells."
   Mol Cancer. 10(4), 11pages (2011).
5. Furumai, R., Uchida, K., Komi, Y., Yoneyama, M., Ishigami, K., Watanabe, H., Kojima, S., and Yoshida, M. :
   "Spliceostatin A blocks angiogenesis by inhibiting global gene expression including VEGF."
   Cancer Science 101(11), 2483-2489 (2010).
6. Mukhopadhyay, B., Liu, J. Osei-Hyiaman, D., Godlewski, G., Mukhopadhyay, P., Wang, L., Jeong, W., Gao, B., Duester, G., Mackie, K., Kojima, S., and Kunos, G.:
   "Transcriptional regulation of cannabinoid receptor-1 expression in the liver by retinoic acid acting via retinoic acid receptor-γ."
   J. Biol. Chem. 285(25), 19002-19011 (2010).
7. Kitazume, S., Imamaki, R., Ogawa, K., Komi, Y., Futakawa, S., Kojima, S., Hashimoto, Y., Marth, D. J., Paulson, C. J., and Taniguchi, N.:
   "α2,6-Sialic Acid on Platelet Endothelial Cell Adhesion Molecule(PECAM) Regulates Its Homophilic Interactions and Downstream Antiapoptotic Signaling."
   J. Biol. Chem. 285(9), 6515-6521 (2010).
8. Komi, Y., Sogabe, Y., Ishibashi, N., Sato, Y., Moriwaki, H., Shimokado, K., and Kojima, S.：
   "Acyclic retinoid inhibits angiogenesis by suppressing the MAPK pathway."
   Lab. Invest. 90(1), 52-60 (2010).
9. Botella, L. M., Rodriguez-Sanz, F., Komi, Y., Fernandez-L, A., Varela, E., Garrido-Martin, E. M., Narla, G., Friedman, S. L., and Kojima, S.:
   "TGF-β regulates expression of KLF6 and its splice variants, and promotes cooperative transactivation of common target genes through a Smad3-Sp1-KLF6 interaction."
   Biochem. J. 419(2), 485-495 (2009).
10. Tatsukawa, H., Fukaya, Y., Frampton, G., Martinez-Fuentes, A., Suzuki, K., Kuo, T.-F., Nagatsuma, K., Shimokado, K., Okuno, M., Wu, J., lismaa, S., Matsuura, T., Tsukamoto, H., Zern, M. A., Graham, R. M., and Kojima, S.：
    "Role of transglutaminase 2 in liver injury via crosslinking and silencing of transcription factor, Sp1."
    Gastroenterology 136(5), 1783-1795 (2009).