生体恒常性の破綻による病態機序を分子レベルで解明し、新規創薬を目指す。 Challenge to elucidation of pathological mechanism caused by breakdown of homeostasis at the molecular level and drug development
教授 五十里 彰Professor Ikari Akira Ph.D.ikari
准教授 遠藤 智史Associate Professor Endo Satoshi Ph.D.sendo
助教 吉野 雄太Assistant Professor Yoshino Yuta Ph.D.yoshino-yu
In this laboratory, we aim to elucidate the molecular mechanisms underlying disease pathogenesis and to provide new diagnosis and treatment based on the findings. Three major projects are described below.
1 . Elucidation of mechanisms underlying abnormal expression of cell adhesion molecules in cancer. Epithelial cells form tight junction (TJ) with neighboring cells. TJ regulates cell proliferation and paracellular transport of molecules. We found that some claudins, TJ proteins, show aberrant expression patterns in cancer cells. We explore oncogenic roles of claudins and develop novel claudin-targeted drugs.
2 . Studies on function, expression, and localization of ion transporters in intestine and skin. Many kinds of ion transporters are expressed in the plasma membrane and each function is mutually regulated by each other. The abnormal expression of transporters was observed in lifestyle-related diseases and disrupts homeostasis in the body. Some ion channels are involved in the regulation of differentiation and barrier in the skin. We aim to elucidate the correlation between dysfunction of transporters and diseases, and develop new medicines.
3 . Development of therapeutic drugs targeting abnormalities in homeostasis. Cells are exposed to various stresses simultaneously, and protein homeostasis is maintained by self-cleaning mechanisms such as proteasome and autophagy and antioxidant mechanisms. Abnormal activation of the mechanisms in cancer cells causes cancer deterioration and anticancer drug resistance. Therefore, we are studying on the development of therapeutic agents that lead to dysregulation of homeostasis in cancers by in silico drug discovery methods and adding functionalities to natural compounds.
研究課題 Research Objectives
癌などの疾患における細胞間接着分子の発現異常機構の解明 Elucidation of mechanisms underlying abnormal expression of cell adhesion molecules in cancer
消化管や皮膚におけるイオン輸送体の機能・発現・局在の制御機構に関する研究 Studies on function, expression, and localization of ion transporters in intestine and skin
恒常性維持機構の異常を標的とした疾患治療薬の開発 Development of therapeutic drugs targeting abnormalities in homeostasis
最近の研究成果 Research Results
Hirota C., Takashina Y., Yoshino Y., Okamoto E., Matsunaga T., Ikari A., Reactive oxygen species downregulate transient receptor potential melastatin 6 expression mediated by the elevation of miR-24-3p in renal tubular epithelial cells., Cells, 10, 1893 (2021).
Ito A., Nasako H., Akizuki R., Takashina Y., Eguchi H., Matsunaga T., Yoshino Y., Endo S., Ikari A., Elevation of chemosensitivity of lung adenocarcinoma A549 spheroid cells by claudin-2 knockdown through activation of glucose transport and inhibition of Nrf2 signal., Int. J. Mol. Sci., 22, 6582 (2021)
Endo S., Nishiyama T., Matuoka T., Miura T., Nishinaka T., Matsunaga T., Ikari A., Loxoprofen enhances intestinal barrier function via generation of its active metabolite by carbonyl reductase 1 in differentiated Caco2 cells. Chem. Biol. Interact., 348, 109634 (2021).
Yoshino Y., Marunaka K., Kobayashi M., Matsunaga H., Shu S., Matsunaga T., Ikari A., Protective effects of ethanol extract of Brazilian green propolis and apigenin against weak ultraviolet ray-B-induced barrier dysfunction via suppressing nitric oxide production and mislocalization of claudin-1 in HaCaT cells., Int. J. Mol. Sci., 22, 10326 (2021).
