We perform 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 recurrence of the cancer.

Main Research Field

Medicine, dentistry, and pharmacy

Related Research Fields

Biology

Keywords

• TGF-β LAP Degradation Products (LAP-D)
• Next Generation Drug Discovery for HBV
• Acyclic Retinoid (Peretinoin)
• Nuclear Transglutaminase
• Diagnosis of Liver Fibrogenesis

Selected Publications

1. Shrestha, R., Shrestha, R., Qin, X-Y., Kou, T.-F., Oshima, Y., Iwatani, S., Teraoka, R., Fujii, K., Hara, M., Li, M., Takahashi-Nakaguchi, A., Chibana, H., Lu, J., Cai, M., Kajiwara, S., and Kojima, S.:
   Fungus-derived hydroxyl radicals kill hepatic cells by enhancing nuclear transglutaminase.
   Sci Rep. 7: 4746. (2017)
2. Tsukuda, S., Watashi, K., Hamada, Y., Isogawa, M., Iwamoto, M., Omagari, K., Suzuki, R., Aizaki, H., Kojima, S., Sugiyama, M., Saito, A., Tanaka, Y., Mizokami, M., Sureau, C., and Wakita, T. :
   A new class of hepatitis B and D virus entry inhibitors, proanthocyanidin and its analogs, that directly act on the viral large surface protein.
   Hepatology 65(4):1104-1116. (2017)
3. Qin, X-Y., Tatsukawa, H., hitomi, K., Shirakami, Y., Ishibashi, N., Shimizu, M., Moriwaki, H., and Kojima, S.:
   "CE/LC-TOFMS-based metabolic analyses uncovered inhibitory effect of acyclic retinoid on aberrant lipogenesis in mouse diethylnitrosamine-induced hepatic tumorigenesis models."
   Cancer Prevention Res. 9(3):205-214.(2016)
4. Shrestha, R., Tatsukawa, H., Shrestha, R., Ishibashi, N., Matsuura, T., Kagechika, H., Kose, S., Hitomi, K., Imamoto, N., and Kojima, S.:
   "Molecular mechanism by which acyclic retinoid induces nuclear localization of transglutaminase 2 in human hepatocellular carcinoma cells."
   Cell Death & Disease, 6, e2002.(2015)
5. Hara, M., Inoue, I., Yamazaki, Y., Kirita, A., Matsuura T., Friedman, S., Rifkin, D.B., and Kojima, S.:
   "L59 TGF-β LAP degradation products serve as a promising blood biomarker for liver fibrogenesis in mice."
   Fibrogenesis Tissue Repair 8:17.(2015)
6. Hara, M., Kirita, A., Kondo, W., Matsuura, T., Nagatsuma, K., Dohmae, N., Ogawa, S.,Imajoh-Ohmi, S., Friedman, S. L., Rifkin, D. B., and Kojima, S.:
   "LAP degradation product reflects plasma kallikrein-dependent TGF-β activation in patients with hepatic fibrosis."
   SpringerPlus 3:221.Doi: 10.1186/2193-1801-3-221 eCollection 2014.(2014)
7. Sakata, K., Hara, M., Terada, T., Watanabe, N., Takaya, D., Yaguchi, S., Matsumoto, T., Matsuura, T., Shirouzu, M., Yokoyama, S., Yamaguchi, T., Miyazawa, K., Aizaki, H., Suzuki, T., Wakita, T., Imoto, M., and Kojima, S.:
   “HCV NS3 protease enhances liver fibrosis via binding to and activating TGF-β type I receptor.”
   Sci. Rep. 3:3243.(2013)
8. 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)
9. 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), 11pagesx.(2011)
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)