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**''Create New World of Bioactive Synthetic Molecules''&br;''New ways to use, New Shapes, New sizes.'' [#m6455066]
As biological processes all stem from chemical events, it should be possible to understand or manipulate biological events by using chemistry. As chemical biologists our challenge is to discover or design unique organic molecules, 'super tools' that modulate fundamental processes in human cells. Using these 2st century super tools we can explore complex cellular events. Our job is creation: designing a new world of bioactive synthetic molecules, with unique and novel uses, forms and sizes. The future for small-molecule applications is open before us, in a range of fields, including future drug discovery and cell therapy. Our 21st century technology and skills will revolutionize the fight against the most difficult diseases and medical challenges of the age.
**''ケミカルバイオロジー～化学を起点とした生物学'' [#c193215c]
ケミカルバイオロジーとは、化学を起点とした生物学です。生命の営みはせんじつめれば化学反応でできています。逆に化学を使って生命現象を理解したり、操ることができるはず。私たちの研究室では、生き物やヒト細胞にユニークな効果を及ぼす独自な有機化合物を見つける、もしくはデザインし、それらを道具として生命現象を探究・操作してきました。生物の仕組みは複雑ですが、有機化合物を起爆剤として用いることで、新たな切り口で生物を研究したり操作することができます。私たちの大きな研究目標は、生理活性合成化合物の新しい世界を切り開くことです。生理活性化合物の新しい利用法、新しいカタチをした生理活性化合物、新しいサイズの生理活性化合物など、アイデアを与えることができればと思うのです。こういったアイデアは、未来の創薬の考え方や化合物の細胞治療への利用などに結びつくはずです。
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*Selected Publications [#jd61e510]
**''Vitamin D metabolite, 25-Hydroxyvitamin D, regulates lipid metabolism by inducing degradation of SREBP/SCAP.'' [#mef7b73d]
***Asano, L., Watanabe, M., Ryoden, Y., Usuda, K., Yamaguchi, T., Khambu, B., Takashima, M., Sato, S., Sakai, J., Nagasawa, K., Uesugi, M. [#hc2fdbc9]
'''''Cell Chem Biol.''''' 24, 207-217 (2017).
|Sterol regulatory element-binding proteins (SREBPs) are transcription factors that control lipid homeostasis. SREBP activation is regulated by a negative feedback loop in which sterols bind to SREBP cleavage-activating protein (SCAP), an escort protein essential for SREBP activation, or to insulin-induced genes (Insigs) (endoplasmic reticulum [ER] anchor proteins), sequestering the SREBP-SCAP-Insig complex in the ER. We screened a chemical library of endogenous molecules and identified 25-hydroxyvitamin D (25OHD) as an inhibitor of SREBP activation. Unlike sterols and other SREBP inhibitors, 25OHD impairs SREBP activation by inducing proteolytic processing and ubiquitin-mediated degradation of SCAP, thereby decreasing SREBP levels independently of the vitamin D receptor. Vitamin D supplementation has been proposed to reduce the risk of metabolic diseases, but the mechanisms are unknown. The present results suggest a previously unrecognized molecular mechanism of vitamin D-mediated lipid control that might be useful in the treatment of metabolic diseases.|#ref(research01.jpg,right,100%)|
