Obihiro University of Agriculture and Veterinary Medicine

• 小型魚類をモデルとした化学物質の有害性評価と毒性発現機構に関する研究
• 希少動物の薬物感受性評価法の確立と投薬応用に関する研究
• 化学物質感受性の種差に関する比較毒性学的研究
• シトクロムP450の生理学的・毒性学的役割および発現制御機構の解明

本学の学生さんには，自然界・生命の現象に幅広い見識を持つということと，興味を持ったテーマを集中的に掘り下げること，この両面にバランスよく柔軟に向き合うことで，確固とした哲学を持ちつつ物事を俯瞰する能力を養ってほしいと思います。こうした努力を続けることで，毒性学に限らず様々な分野において，学際性・専門性の高い研究に取り組むための素地をつくることができると思います。

毒性学研究室ではとくに研究職志望の学生さんを歓迎します。生命科学的アプローチによる毒性学研究に興味を持った方であればユニットは問いません。「こういう研究がやりたいけどできるか」とか「研究者として将来海外で研鑽を積みたいけど何から始めたらよいか」などありましたら気軽にお問い合わせください。

Major research topics in our research group are as follows:

1. Understanding adverse effects and toxic mechanisms of chemical substances using zebrafish as a model species
   You may wonder why zebrafish is being used in a field of veterinary sciences at OUAVM. To date zebrafish have been extensively used as a vertebrate model species in a stunning array of research projects in embryology and medical science. In concurrence with daphnia and algae, zebrafish have been used also for assessing chemical effects on ecosystem. Benefit to using zebrafish as a model for those research subjects includes 1) high homology to human and other mammals at a genomic level, 2) having feature of high fecundity and rapid development with transparency, making it possible to observe organogenesis, 3) ease of genetic manipulation and inhibition of gene function, etc.
   In case livestock animals are exposed heavily to chemical substances such as pesticides, antibiotics, mycotoxins, and environmental contaminants, decline of their productivity may be of great concern. High levels of exposure may also cause adverse human health effects via consumption of livestock products that are contaminated with those chemicals. Alternatively, exposure of wildlife to those chemicals may cause detrimental effects on ecosystem through the population decline. In our laboratory, we investigate hazard assessment and toxic mechanism of anthropogenic and natural compounds that potentially threat food safety as well as human and animal health, aiming at contribution to improving animal, food, and environmental hygiene.
2. Development of assessment method for drug sensitivity in endangered species, aiming at clinical application
   In veterinary medicine of wild animals including endangered ones, there often is difficulty in choice of drugs and dosage regimen, due largely to species difference in susceptibility and response to drugs. A key strategy to address these issues is to establish an effective dosage regimen based upon species-specific pharmacokinetics and pharmacodynamics (PK/PD). However, it is difficult to evaluate drug sensitivity and PK/PD as basic information in endangered species because of challenges for conducting administration test with live animals as well as limited availability of fresh tissue samples to work on drug-metabolizing enzymes. Our approach to address these issues is, with the assistance of zoo, 1) to heterologously express (in yeast or bacteria) drug-metabolizing enzymes (e.g., cytochrome P450) that are predominant in liver of a particular species, 2) to examine potency of the expressed enzymes to metabolize drugs that are frequently used in clinical practice and inhibitory effects of drugs on the enzyme functions, and 3) to predict dosage and administration based upon data from those in vitro studies and establish the appropriate dosage regimen through the clinical application with injured or diseased individuals.

• Understanding adverse effects and toxic mechanisms of chemical substances using zebrafish as a model species
• Development of assessment method for drug sensitivity in endangered species aiming at clinical application
• Comparative toxicology toward understanding species difference in susceptibility to chemical substances
• Physiological and toxicological roles and regulation of cytochrome P450
• Surveillance of mycotoxins contamination in corn for animal consumption