客員教授
佐々木 隆造（ささき・りゅうぞう）
Ryuzo Sasaki
専門分野／応用生命科学
職位：客員教授
学位：農学博士（京都大学）
- 京都大学農学研究科博士課程修了
- 京都大学農学部、同大学農学研究科教授、同生命科学研究科教授、滋賀県立大学人間文化学部教授を歴任。京都大学名誉教授、滋賀県立大学名誉教授
研究テーマ
新規がん遺伝子の探索、分子標的抗がん剤の開発と作用の解析
（１）新規がん遺伝子の探索：野生型酵母あるいは特定の変異型酵母にヒトcDNAを導入し、酵母の増殖阻害を指標にしてスクリーニングを行う（ヒト化酵母プロジェクト）。特に、酵母の増殖阻害を引き起こす機能未知のヒト遺伝子に着目している。すでに、特定の変異型酵母の増殖阻害を引き起こす機能未知のヒト遺伝子C18orf26を発見し、新規なガン遺伝子であることを示す証拠を蓄積した。
（２）ヒストン脱メチル化酵素類の阻害剤を探索している。
（３）抗がん作用のある化合物GEX1Aの細胞増殖抑制活性はスプライシング阻害によることを証明し、その標的分子はスプライソソーム成分SAP155であることを証明した。
Topics of research
(1) Screening of new oncogenes by the use of yeast growth. There are a number of human genes whose functions remain unknown. We have searched human genes that repress growth of the wild-type yeast and mutant yeasts. C18orf26 encoding a protein with unknown function repressed growth of a mutant yeast but not the wild-type yeast. We have evidence showing that this protein (named dynAP) is oncogenic. Screening of new oncogenes by the similar strategy is being continued.
(2) Histone demethylases have been shown to be deeply involved in human diseases including cancer through regulation of gene transcription. By designing small molecules based on structures of demethylase proteins and their substrates, we have found chemicals that inhibit histone demethylases in cells.
(3) GEX1A is a microbial product with antitumor activity, arrests cell cycle at G1 and G2/M phases. We have found that GEX1A exhibits its inhibition of cell proliferation through inhibition of splicing. GEX1A binds to SAP155 protein, a subunit of SF3b responsible for pre-mRNA splicing.
主な業績論文等
- Hasegawa M. et al., Identification of SAP155 as the target of GEX1A (herboxidiene), an antitumor natural product. ACS Chem Biol, 6, 229-233 (2011).
- Sekigawa M. et al., Comprehensive screening of human genes with inhibitory effects on yeast growth and validation of a yeast cell-based system for screening chemicals. J. Biomol. Screen. 15, 368-378 (2010).
- Kunoh T. et al., A novel human dynactin-associated protein, dynAP, promotes activation of Akt, and ergosterol-related compounds induce dynAP-dependent apoptosis of human cancer cells. Mol Cancer Ther. 9, 2934-2942, 2010
- Ueda R. et al., Identification of cell-active lysine specific demethylase1-selective inhibitors. J. Am. Chem. Soc. 131, 17536-17537 (2009).
- Sasaki R. et al., Pleiotropic functions and tissue-specific expression of erythropoietin News in Physiol. Sci. 16, 110-113 (2001).