Our research mission
To clarify the transport characteristics of drug transporters that affect the absorption, distribution, metabolism and excretion (ADME) of drugs/endogenous substances, and to explore the factors that affect the transport activity, leading to a quantitative understanding of inter-individual variability in human clinical pharmacokinetics.Examples of recent research
Research on basic characterization of transport via folate transporter (PCFT)
Folic acid, one of the most important vitamins, is efficiently taken up into cells despite its extremely hydrophilicity, and the importance of transporter in the transport of folic acid has been clarified. In particular, PCFT (proton-coupled folate transporter) plays a major role in the intestinal absorption of folic acid. In order to clarify the basic characteristics of PCFT-mediated transport and the factors that cause inter-individual variation in PCFT transport in clinical situation, we are conducting research on stereoselectivity of substrates, interactions between drugs and food-derived components, and variation in transport caused by genetic mutations.
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Research on basic characterization of transport of organic anions via OATP2B1
OATP (organic anion transporting polypeptide) 2B1 is a transporter that recognizes a wide variety of anionic drugs and is expressed in the gastrointestinal tract, suggesting that it may contribute to the enhancement of intestinal absorption of substrate drugs. In order to clarify the basic characteristics of OATP2B1-mediated transport and the factors that cause inter-individual variability in OATP2B1-mediated transport in the clinical situation, we are conducting research on interactions between drugs and food-derived components and variability in transport caused by genetic mutations.
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Establishment of a culture system for intestinal epithelial stem cells and studies on species difference and regional difference in intestinal drug absorption/expression of gastrointestinal toxicity in differentiated cells
Due to differences in the expression profiles of metabolic enzymes and transporters,
there is no cell system that can accurately predict intestinal absorption
in humans. There are many difference In this study, we are developing a
3D stable culture system of gastrointestinal stem cells as a starting point
for predicting gastrointestinal absorption in humans by using appropriately
differentiated human and animal absorption epithelial cells. In addition,
this cell system maintains the genetic profile of the original cell location
from which the cells were harvested, making it possible to examine differences
in the gastrointestinal tract that were previously impossible to evaluate
in vitro. In addition, since the same cell line can be established from
animals with almost the same protocol, it is also possible to study species
differences in vitro, and we hope to demonstrate the usefulness of this
cell line as an alternative method for animal experiments in the future.
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現在進行中の共同研究・参画プロジェクト
★TaNeDS Project（第一三共（株））
医薬品により誘発される消化管障害を包括的に予測可能な動物実験代替を目指したin vitro実験系・評価法の開発
★日本赤十字社近畿ブロック血液センター（献血血液の研究利用）
分子標的型の抗がん剤による急性の薬剤誘導性貧血のin vitro評価法の確立、原因探索、およびBCRP欠損Jra(-)型赤血球における薬物の分布・副作用との連関に関する研究
本プロジェクトの詳細はこちら (31J0030)
★（公財）実験動物中央研究所 (BINDS)
ヒト肝細胞を有するヒト肝キメラマウス(TK-NOG Hu-Liver mouse)より単離した肝細胞を用いた薬物の肝胆系輸送の定量的予測に関する研究
★LINC（ライフインテリジェンスコンソーシアム）
創薬の様々な局面にAI、機械学習の技術を導入することで、予見性を飛躍的に高める技術開発（前田は、WG07「ADMET, translational research」のワーキンググループ長をつとめている）
本プロジェクトの詳細はこちら