堀部 智久
(ほりべ・ともひさ)
Tomohisa Horibe
略歴
- 立命館大学大学院理工学研究科 博士後期課程修了
- 豪州博士研究員、京都大学大学院医学研究科 特定助教、特定講師、特定准教授を経て本学へ
生体物質科学研究室
卒業研究テーマ例
- fLuc-GFPノックインメダカを用いたPDI familyタンパク質の発生における発現機構の解析
- 天然物由来ケミカルシャペロンによるがん細胞からの細胞外ベシクル産生への影響に関する研究
- ゲノム編集技術により作成した小型魚類および生物発光を用いた生殖発生毒性の評価系の構築
ゲノム編集技術を用いたPDI familyタンパク質のin vivo解析
天然物由来ケミカルシャペロンの新たな効能、薬効の評価
小型魚類および生物発光を用いた新たな薬剤評価系およびスクリーニングプラットフォームの構築
- 研究の応用領域
- 医薬品の開発、新たな創薬のための新技術開発
- 産官学連携で求めるパートナー
- 医薬品・診断薬および、化粧品開発に取り組んでいる企業、養殖魚関連企業、バイオ機器メーカー、大学、国・地方自治体の基礎研究機関
It is known that the bioluminescence based on the reaction of luciferin and luciferase (Luc) has several advantages such as (i) low background and higher quantification, (ii) lower photo-toxicity since it is not necessary to use excitation light, and (iii) longer observation compared with that of green fluorescence protein (GFP). In this biomaterial science laboratory, we focus on the function of molecular chaperones in the cells, and try to establish the new evaluation methods of drug candidates using small freshwater fish such as medaka and zebrafish by bioluminescence imaging at single cell level through the research themes as described below.
Functional analysis of protein disulfide isomerase family proteins in vivo by genome editing.
It is still obscure about the detailed physiological roles of protein disulfide isomerase (PDI) family proteins in vivo. Thus, we try the functional analysis of these proteins by the knock-down using genome editing in medaka and zebrafish. In addition, we try to perform the knock-in of firefly Luc-GFP by the genome editing, and evaluate the expression patterns of these proteins in the fish.
Evaluation of chemical chaperones derived from natural products
It is known that several foods and plants contain compounds, which have the activities of chaperone-like and anti-oxidant in the cells such as ferulic acid, kojic acid and rutin. We try to evaluate the function of these compounds as new drug candidates in cancer cells. We also explore the application to production of aquaculture fish with new nutrients using these chemical chaperones as fish bait.
Establishment of new evaluation and screening methods for drug candidates by bioluminescence imaging.
We try to establish the new platform of evaluation and screening methods for drug candidates using small fish such as medaka and zebrafish by bioluminescence imaging at single cell level, in which we use not only firefly luciferase but also small nanoLuc luciferase derived from deep sea shrimp.
Murakami, Y., Futamata, R., Horibe, T., Ueda, K., and Kinoshita, M. (2020)
CRISPR/Cas9 nickase-mediated efficient and seamless knock-in for lethal genes in medaka fish (Oryzias latipes). Dev Growth Differ 62, 554-567.Kohno, M., Musashi, K., Ikeda, O., H., Horibe, T., Matsumoto, A., and Kawakami, K. (2020) Oral administration of ferulic acid or ethyl ferulate attenuates retinal damage in sodium iodate-induced retinal degeneration mice. Sci Rep 10, 8688.
Murakami, Y., Horibe, T., and Kinoshita, M. (2019) Development of an efficient bioreactor system for delivering foreign proteins secreted from liver into eggs with a vitellogenin signal in medaka Oryzias latipes. Fisheries Science 85, 677-685.
Kurihara, R., Horibe, T., Shimizu, E., Torisawa, A., Gaowa, A., Kohno, M., and Kawakami, K. (2019) A novel interleukin-13 receptor alpha 2-targeted hybrid peptide for effective glioblastoma therapy. Chem Biol Drug Des 94, 1402-1413.
Horibe, T., Okushima, N., Torisawa, A., Akiyoshi, R., Hatta-Ohashi, Y., Suzuki, H., and Kawakami, K. (2018) Evaluation of chemical chaperones based on the monitoring of Bip promoter activity and visualization of extracellular vesicles by real time bioluminescence imaging. Luminescence 33, 249-255.