三輪 正直
(みわ・まさなお)
Masanao Miwa
略歴
- 東京大学医学部卒
- 国立がんセンター研究所ウイルス部長、副所長、筑波大学教授、同大学院医学研究科長、基礎医学系長、同人間総合科学研究科教授を歴任。
- 筑波大学名誉教授。
タンパク質の翻訳後修飾:ポリADP-リボシル化反応の意義
発がんにおける中心体の役割の解明と診断への応用
感染症(肝吸虫)と胆管がん発症機構の解明と早期診断のための腫瘍マーカーの開発
- 研究の応用領域
- がんの補助診断薬の開発
- 産官学連携で求めるパートナー
- 診断薬開発の関連企業
Posttranslational protein modification: Biological significance of polyADP-ribosylation
PolyADP-ribosylation is one of the posttranslational modifications and is involved in regulation of DNA repair, transcription, genomic stability, centrosome function, differentiation, cell death and carcinogenesis. We are studying the roles on carcinogenesis (Miwa, M. and Masutani, M. Cancer Sci. 98: 1528-1535(2007)) and neuronal degeneration (Hanai, S. et al. Proc. Natl. Acad. Sci. USA 101: 82-86 (2004)). We have developed an ELISA system to measure in vivo level of poly(ADP-ribose) to better understand the function of polyADP-ribosylation in various physiological conditions.
Mechanism of centrosome amplification in carcinogenesis
Chromosome abnormality has been long known in cancer cells. Recently centrosome amplification (abnormal number of centrosomes) was known in many cancer cells (Miwa, M. and Masutani, M. Cancer Sci. 98: 1528-1535 (2007)). We found that inhibitors of polyADP-ribosylation or knockout of poly(ADP-ribose) polymerase 1 gene induced centrosome amplification (Kanai, M. et al. Mol. Cell. Biol. 23: 2451-2462 (2003)).
Infection and cancer prevention
Infection with the liver fluke (Opisthorchis viverrini (OV)) has been common and related to cholangiocarcinoma in the northeast Thailand. However, less than 10% of the inhabitants develop cholangiocarcinoma, and animal experiments suggest the OV infection alone does not cause the cholangiocarcinoma. Other environmental and genetic factors may play an additional role in the causation. We studied the involvement of the genetic background in cholangiocarcinogenesis. We found combined effects of polymorphisms of DNA repair protein genes and metabolic enzyme genes for risk of cholangiocarcinoma (Zeng, L. et al. Jpn. J. Clin. Oncol. 43: 1190-1194 (2013)). We are trying to develop a tumor marker in the blood for cholangiocarcinoma (Miwa, M. et al. J. Hepatobiliary Pancreat. Sci. 21(6): 397-398 (2014)).
Miwa, M., Ida, C., Yamashita, S., Tanaka, M., Fujisawa, J. Poly(ADP-ribose): Structure, physicochemical properties and quantification in vivo, with special reference to poly(ADP-ribose) binding protein modules. Curr Protein Pept Sci. 17(7): 683-692 (2016).
Ida, C., Yamashita, S., Tsukada, M., Sato, T., Eguchi, T., Tanaka, M., Ogata, S., Fujii, T., Nishi, Y., Ikegami, S., Moss, J., Miwa, M. An enzyme-linked immunosorbent assay-based system for determining the physiological level of poly(ADP-ribose) in cultured cells. Anal Biochem. 494: 76-81 (2016).
Yamashita S, Tanaka M, Sato T, Ida C, Ohta N, Hamada T, Uetsuki T, Nishi Y, Moss J, Miwa M. Effect of mild temperature shift on poly(ADP-ribose) and γH2AX levels in cultured cells. Biochem Biophys Res Commun. 476(4): 594-599 (2016).
Miwa, M., Honjo, S., You, G., Tanaka, M., Uchida, K., Srivatanakul, P., Khuhaprema, T., Loilome, W., Techasen, A., Wongkham, C., Limpaiboon, T., Yongvanit, P., Wongkham, S. Genetic and environmental determinants of risk for cholangiocarcinoma in Thailand. World J. Gastrointest. Pathophysiol. 15;5(4):570-578 (2014).
Miwa, M., You, G., Tanaka, H., Taniguchi, S., Fujii, T., Kamemura, K., Suzaki, M., Isono, T., Tooyama, I., Tanaka, M., Srivatanakul, P., Viwatthanasittiphong, C.,Sangrajrang, S., Khuhaprema, T. Analysis of new biomarkers for cholangiocarcinoma. J. Hepatobiliary Pancreat. Sci. 21(6):397-398(2014).