RIKEN Center for Integrative Medical Sciences
Micro-Signaling Regulation Technology Unit
Unit Leader: Soichi Kojima (Ph.D.)
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
- 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) - 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) - 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) - 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) - 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) - 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) - 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) - 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) - 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) - 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)
Lab Members
Principal Investigator
- Soichi Kojima
- Unit Leader
Core Members
- Yutaka Furutani
- Research Scientist
- Ryutaro Teraoka
- Postdoctoral Researcher
- Xian-Yang Qin
- Postdoctoral Researcher
- Senko Tsukuda
- Postdoctoral Researcher
- Mitsuko Hara
- Research Associate
- Mengqian Li
- International Program Associate
- Emi Takano
- Technical Staff I
- Ikuyo Inoue
- Technical Staff 1
- Mariko Toguchi
- Technical Staff I
- Yumi Sato
- Technical Staff I
- Yukari Matsuba
- Assistant
- Kimie Tajima
- Assistant