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.
- Studies on development of anticancer drugs. Cancer cells exhibit gene expression profiles distinct from the normal cells. Recent reports show that some membrane proteins constituting intercellular junction and enzymes involved in steroid and glucose metabolism are highly expressed in cancer cells and function as key regulators in cell proliferation as well as chemo-resistance. We explore oncogenic roles of the target proteins and rationally develop new potent and specific inhibitors based on their tertiary structures.
- Studies on regulatory mechanisms of function, expression, and localization of ion transport systems in renal tubule. In the kidney, blood is filtered in the glomerulus and then water, electrolyte, and amino acid are reabsorbed in the renal tubules. Many kinds of ion channels and transporters are expressed in the tubule and each function is mutually regulated by each other. We aim to elucidate the molecular mechanisms underlying hypomagnesemia and develop new medicines.
- Elucidation of pathobiochemical role of oxidized-lipoproteins in atherogenic mechanism. It is widely accepted that formation of oxidized LDL is a crucial step for onset of atherosclerosis, whereas little is understood about oxidation of HDL and its role in the disease-related alterations. In previous experiments, we found that the blood level of oxidized HDL is significantly higher in patients with atherosclerosis, suggesting that oxidized HDL, like oxidized LDL, and plays a key role in the pathogenesis of atherosclerosis.
- Elucidation of mechanisms underlying abnormal expression of cell adhesion molecules in cancer
- Studies on regulatory mechanisms of function, expression, and localization of ion transport systems in renal tubule
- Elucidation of pathobiochemical role of oxidized-lipoproteins in atherogenic mechanism
- Studies on development of drug targeted to xenobiotic-detoxifying enzymes
- Sonoki H., Sato T., Endo S., Matsunaga T., Yamaguchi M., Yamazaki Y., Sugatani J., Ikari A., Quercetin decreases claudin-2 expression mediated by up-regulation of microRNA miR-16 in lung adenocarcinoma A549 cells., Nutrients, 7, 4578-4592 (2015).
- Morikawa Y., Kezuka C., Endo S., Ikari A., Soda M., Yamamura K., Toyooka N., El-Kabbani O., Hara A., Matsunaga T., Acquisition of doxorubicin resistance facilitates migrating and invasive potentials of gastric cancer MKN45 cells through up-regulating aldo-keto reductase 1B10, Chem. Biol. Interact., 230, 30-39 (2015).
- Endo S., Nishiyama A., Suyama M., Takemura M., Soda M., Huayue C., Tajima K., El-Kabbani O., Bunai Y., Hara A., Matsunaga T., Ikari A., Protective roles of aldo-keto reductase 1B10 and autophagy against toxicity induced by p-quinone metabolites of tert-butylhydroquinone in lung cancer A549 cells, Chem. Biol. Interact., 234, 282-289. (2015).