Field of Study
Molecular Toxicology, Endocrinology
Keywords
Risk assessment, Endocrine disruptors, Developmental neurotoxicity, Immunotoxicity, Nuclear receptors, Reporter mouse, PCOS
Lab URL
https://sites.google.com/gifu-pu.ac.jp/eisei-nakanishilab
生命科学技術を駆使し、化学物質を安全に使用できる社会の実現に貢献する
Commitment to creating a sustainable society in which chemical substances can be used safely through the application of novel life science technologies
  • 教授 中西 剛 Professor Nakanishi Tsuyoshi Ph.D. nakanishi
  • 准教授 松丸 大輔 Associate Professor Matsumaru Daisuke ph.D. matsumaru-da
  • 助教 石田 慶士 Assistant professor Ishida Keishi Ph.D. ishida

研究テーマ Research Subjects

 衛生学研究室では、化学物質のリスクアセスメントへの貢献を念頭に、化学物質の毒性発現機構の解明や安全性評価を行うための試験法の開発を、遺伝子改変モデル動物や分子生物学的手法、イメージング技術を用いて行っている。また現在もなおその健康影響が懸念されている内分泌かく乱化学物質問題の解決を図るために、核内受容体を介した生体影響に関する研究や性分化機構および性分化疾患の解明に関する研究を行っている。さらに当研究室では、「核内受容体を介した化学物質の生体影響に関する研究」について中国(北京大学)およびポルトガル(ポルト大学)との国際共同研究を積極的に展開している。北京大学との共同研究では、強力な抗エストロゲン作用を示すフルオレン- 9 - ビスフェノール(BHPF)がペットボトルの飲料水中に存在し、生殖発生毒性を誘発する可能性を見出した。BHPF についてはその曝露リスクや毒性に関する報告が全くなかったことから、Nature Communication 誌に掲載された当該データが Nature Asia Website のハイライト等に取り上げられ、世界的にも注目を集めている。

For contributing to toxicology, especially risk assessment of chemical substances, we are analyzing toxicological mechanisms and developing a novel toxicity test method of chemical substances using molecular biological techniques, imaging technology and transgenic animals. In addition, to solve the problem of endocrine disrupting chemicals which are still concerns for health hazards, we are also conducting research on biological impacts via nuclear receptors and on the mechanisms of sex development and its related diseases. Furthermore, we are conducting international collaborative research with China (Peking University) and Portugal (University of Porto) on "the biological impacts of chemical substances via nuclear receptors". By the joint research with Peking University, we found that the Fluorene- 9 -bisphenol (BHPF), a potent anti-estrogen, is present in the drinking water of plastic bottles and can induce reproductive toxicity. Since the toxicity of BHPF had not been understood at all, our paper published in Nature Communication was highlighted in the Nature Asia website and it is still attracting worldwide attention now.

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研究課題 Research Objectives

  1. 核内受容体を介した化学物質の生体影響に関する研究
    Studies on the biological impacts of chemical substances via nuclear receptors
  2. イメージング技術を応用した新規毒性評価手法の開発
    Development of a novel toxicity test method using imaging technology
  3. 性分化および性分化疾患に関する研究
    Studies on the mechanisms of sex development and disorders of sex development
  4. 生体の環境応答と疾患との関わりに関する研究
    Studies on the relationship between diseases and stress induced environmental responses
  5. 化学物質による皮膚感作性および免疫機能修飾機構の解明
    Studies on the mechanism of skin sensitization and immune system modification by chemicals

最近の研究成果 Research Results

  1. Ishida K. †, Tatsumi K. †, Minamigawa Y., Mori K., Matsumaru D., Nagase H., Kanda Y., Takuma K., Nakanishi T. Neuronal differentiation reporter mice as a new methodology for detecting in vivo developmental neurotoxicity. Biochem. Pharmacol., 206, 115332 (2022) († Equal contribution).
  2. Capitão AMF., Lopes-Marques MS., Páscoa I., Sainath SB., Hiromori Y., Matsumaru D., Nakanishi T., Ruivo R., Santos MM., Castro LFC., An ancestral nuclear receptor couple, PPAR-RXR, is exploited by organotins. Sci. Total Environ. 797, 149044 (2021).
  3. Yoshida, I.†, Ishida, K.†, Yoshikawa, H., Kitamura, S., Hiromori, Y., Nishioka, Y., Ido, A., Kimura, T, Nishikawa, J.I., Hu, J., Nagase, H., Nakanishi, T., In vivo profiling of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced estrogenic/ anti-estrogenic effects in female estrogen-responsive reporter transgenic mice, J. Hazard. Mater., 385, 121526 (2020) († Equal contribution).
  4. Uruno, A.†, Matsumaru, D.†, Ryoke, R., Saito, R., Kadoguchi, S., Saigusa, D., Saito, T., Saido, TC., Kawashima, R., Yamamoto, M., Nrf2 suppresses oxidative stress and inflammation in app knock-in Alzheimer's disease model mice, Mol. Cell. Biol., 40, e00467-19 (2020) († Equal contribution).
  5. Zhang, Z., Hu, Y., Guo, J., Yu, T., Sun, L., Xiao, X., Zhu, D., Nakanishi, T., Hiromori, Y., Li, J., Fan, X., Wan, Y., Cheng, S., Li, J., Guo, X., Hu, J., Fluorene-9-bisphenol is anti-oestrogenic and may cause adverse pregnancy outcomes in mice, Nat. Commun., 8, 14585 (2017).