Main Research Interests
- Relevance of transporters and their adaptor proteins to pharmacotherapeutics and human diseases
- Cell-specific membrane permeation mechanism(s) relevant to drug delivery
- Optimization of drug therapy and clinical trial based on PBPK theory
Outlines of Researches
Our research focuses on physical interaction among transporters, enzymes and pharmacological/toxicological target proteins.
Homeostasis can be maintained by simultaneous cooperation between absorption of nutrients and secretion of xenobiotics. A large number of xenobiotic transporters and metabolic enzymes are possibly involved in recognition and subsequent influx/efflux/detoxification of nutrients and xenobiotics. However, we still do not know exact mechanisms which can explain efficient absorption of many therapeutic agents, implying the presence of unknown molecular machinery for the specific recognition.
We have already specified adaptor proteins (PDZK1, Rab8) which play pivotal roles in localization and/or function of xenobiotic transporters. Since those adaptors can also interact with enzymes, channels and receptors, our preliminary findings may propose formation of macromolecular complex composed of those proteins interacting with adaptors. Such protein-protein network may partially explain how the body maintains homeostasis by recognizing nutrients, xenobiotics and therapeutic agents.
We are attempting to clarify pharmacological/toxicological roles of not only transporters or other enzymes, but also such protein complex formed via adaptor proteins. We are also attempted to extrapolate phenotypes observed in vivo from in vitro data and subsequently predict final efficacy and toxicity of drugs in humans based on physiologically-based pharmacokinetic/pharmacodynamic (PB-PK/PD) theory.
Main References
- Kato Y, Sugiura T, Nakadera Y, Sugiura M, Kubo Y, Sato T, Harada A, Tsuji A. Investigation of the role of oligopeptide transporter PEPT1 and sodium/glucose cotransporter SGLT1 in intestinal absorption of their substrates using small GTP-binding protein Rab8 null mice. Drug Metab Dispos, 37(3): 602-607, 2009.
- Kano T, Kato Y, Ito K, Ogihara T, Kubo Y, Tsuji A. Carnitine/organic cation transporter OCTN2 (Slc22a5) is responsible for renal secretion of cephaloridine in mice. Drug Metab Dispos, 37(5): 1009-1016, 2009.
- Kato Y, Miyazaki T, Kano T, Sugiura T, Kubo Y, Tsuji A. Involvement of influx and efflux transport systems in gastrointestinal absorption of celiprolol. J Pharm Sci, 98(7): 2529-2539, 2009.
- Sugiura T, Kato Y, Wakayama T, Silver DL, Kubo Y, Iseki S, Tsuji A. PDZK1 regulates two intestinal solute carriers (Slc15a1 and Slc22a5) in mice. Drug Metab Dispos, 36(6): 1181-1188, 2008.
- Sato T, Mushiake S, Kato Y, Sato K, Sato M, Takeda N, Ozono K, Miki K, Kubo Y, Tsuji A, Harada R, Harada A. The Rab8 GTPase regulates apical protein localization in intestinal cells. Nature 448(7151): 366-369, 2007.
Staffs
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Yukio KATO Professor
Specialized field
Pharmacotherapeutics, Drug Disposition and Delivery
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Noritaka NAKAMICHIAssociate Professor
Specialized field
Pharmacotherapeutics, Cellular Pharmacodynamics, Cellular Pharmacology
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Tomoko SUGIURA Assistant Professor
Specialized field
Pharmacotherapeutics, Drug Disposition and Delivery, Transporter