トップページ研究室紹介(統合医薬学領域)分子医薬学 トキシコゲノミクス

分子医薬学

トキシコゲノミクス

トキシコゲノミクス/Drug Safety Sciencesの独自ホームページはこちら

研究室概要

  トキシコゲノミクス研究室という名前は、聞き慣れないことと思います。名古屋大学大学院医学系研究科は、平成25年度より「総合医学専攻」という単一専攻に組織改革を行い、これに伴って基礎医学と臨床医学の領域に、新たに「統合医薬学領域」が加わり、三領域体制になりました。この統合医薬学領域は創薬を主たるkey wordとして研究と教育を充実させ、優れた人材の輩出と研究成果を期待されています。こうした背景から、「トキシコゲノミクス」研究室、和訳をしますと「毒性遺伝子学」、という名称の『医薬品の安全性科学』を専門とする研究室が新たにスタートしました。  

  日常的に処方される薬による症状改善の程度は個人によって著しく異なり、疾病によっては半分以上の患者様に薬効が認められない場合もめずらしくありません。全体の約10%のヒトに何らかの副作用が発現しているという米国FDA(Food and Drug Administration)の統計もあります。1992年の米国の統計では、薬に起因する死亡が死因の4番目であると報告され、薬の副作用による社会的損失は膨大なものであり、その頃から、薬の安全性を確保する研究の必要性が強く認識されるようになりました。薬の副作用や毒性において、その予測や回避が難しい場合において、そのほとんどのケースは、薬の薬理や薬効に全く関係なく発現します。副作用の発現を説明するには、薬が全身でどのように移動し、解毒されるか、また薬の構造変換と毒性の関わりを理解する必要があります。すなわち、「薬物動態」分野の研究領域になります。

  近年の薬物動態分野の研究の顕著な発展に伴って、創薬段階における臨床試験での開発中止が、薬物動態に起因するケースは、1991年、2000年、2011年で、40%、9%、1%へと激減してきています。しかし、副作用・毒性発現に起因する開発中止のケースは、13%、20%、19%と高水準のままであり、とりわけ、市販後に予期せぬ副作用の発現によって撤退・発売停止のケースも含めて、その原因は薬物性肝障害の発症が最も多いことが知られています。よって、厚生労働省のみならず、FDAやEUにおいても、予測が難しい薬物性肝障害の解明研究が特別推進課題と位置づけられています。 

  近年、医薬品の安全性を確保するための、薬物動態及び薬物代謝の研究には、ゲノムのみならず、メッセンジャーRNA、蛋白質、マイクロRNAの広汎な理解に加え、リン酸化や脱アセチル化等の因子や食事や生活のストレスの影響等の理解も必要であることが明らかにされつつあり、極めて幅広い研究が必要になっています。こうした背景から、横井毅は金沢大学大学院薬学系の教授として16年間、薬物代謝と毒性の研究を行ってきました。その経験をさらに発展させ、「トキシコゲノミクス」研究室では、薬による副作用の研究を中心に、主に薬物性肝障害の基礎および臨床研究を充実させて行きたいと考えています。特に免疫学的因子と、極めて初期に応答するマイクロRNAを考慮した、肝障害発症機序の包括的理解と、その予測試験系の構築を目指します。さらに、安全性に関わる基礎的研究のみならず、臨床での様々な薬に関連する問題を解決する研究課題を設定し、薬を通して直接臨床に資する研究を目指したいと考えています。加えて、他機関との共同研究、臨床共同研究のみならず、製薬会社、CRO、規制当局も集う、情報交換と情報発信の場の形成を目指し、その為には、研究内容の重要性や社会性を広く発信し、多くの研究員や学生がインタラクションする研究環境を創設したいと考えています。

教員紹介

構成員名/英名表記 役職 所属
横井 毅/YOKOI Tsuyoshi
詳しくはこちら→
教授トキシコゲノミクス
中島 晶/NAKAJIMA Akira
詳しくはこちら→
講師トキシコゲノミクス
織田 進吾/ODA Shingo
詳しくはこちら→
特任助教トキシコゲノミクス

研究分野紹介

専攻 総合医学専攻
大講座 分子医薬学
分野 トキシコゲノミクス

研究キーワード

薬の副作用、薬物代謝、薬物動態、肝障害、臓器障害、動物モデル、毒性発現予測、non-coding RNA、免疫毒性、医薬品トキシコロジー、医薬品安全性学、毒性学

修士課程・博士課程に入学を希望される方へ

◆修士課程2年コースの『医科学修士課程』と、博士課程3~4年コースの『医学博士課程』があります。

 

 

  薬の解毒や副作用発現メカニズムの解明や安全性予測の研究に、少しでも興味のある方は是非連絡をください。見学歓迎です。入試制度や研究内容など、何でもお気軽に連絡を頂ければ幸いです。

  研究は薬に関する内容が主ですが、みなさんの出身学部は問いません。日本には多くの製薬会社がありますが、その研究者が薬学出身である割合は約30%程度です。約70%は農学部、理学部、工学部や獣医学部などの出身の研究者です。製薬企業のみならず、化粧品や食品関連企業等にも、安全性の研究者は必要とされています。

  「どんな研究をしているのだろう?」「どんな雰囲気の研究室だろう?」「キャリアパスは?」など、少しでも関心をお持ちの方は、気軽にご連絡をください。

 

 

入学試験情報はこちら→『修士課程入試案内』、『博士課程入試案内

連絡先

〒466-8550 名古屋市昭和区鶴舞町65

名古屋大学大学院医学系研究科トキシコゲノミクス

Tel: 052-744-2110,  Fax: 052-744-2114

横井毅 tyokoiの後ろに@をつけてmed.nagoya-u.ac.jpです。

 

場所:医系研究棟3号館7階 (714)

 

最近の業績

2015

原著論文

1) Eita Sasaki, Azumi Iida, Shingo Oda, Koichi Tsuneyama, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. Pathogenetic analyses of carbamazepine-induced liver injury in F344 rats focused on immune- and inflammation-related factors. Exp. Toxicol. Pathol., in press (2015). 

 

2) Sho Akai, Yasuaki Uematsu, Koichi Tsuneyama, Shingo Oda, and Tsuyoshi Yokoi. Kupffer cell-mediated exacerbation of methimazole-induced acute liver injury in rats. J. Appl. Toxicol., in press (2015).

 

3) Akira Nakajima, Yuki Aoyama, Eun-Joo Shin, Yunsung Nam, Hyoung-Chun Kim, Taku Nagai, Akihito Yokosuka, Yoshihiro Mimaki, Tsuyoshi Yokoi, Yasushi Ohizumi, and Kiyofumi Yamada. Nobiletin, a citrus flavonoid, improves cognitive impairment and resuces soluble Ab levels in a triple transgenic mouse model of Alzheimer’s disease (3XTg-AD). Behav. Brain. Res., 289: 69-77 (2015).

 

4) Takafumi Tomida, Hayao Okamura, Masahiro Satsukawa, Tsuyoshi Yokoi, Yoshihiro Konno. Mutipaprmetric assay using HepaRG cells for predicting drug-induced liver injury. Toxicol. Lett., 236: 16-24 (2015).

 

5) Azumi Iida, Eita Sasaki, Azusa Yano, Koichi Tsuneyama, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. Carbamazepine-induced liver injury requires CYP3A-mediated metabolism and glutathione depletion in ratsDrug Metab. Dispos., 43: 958-968 (2015).

 

6) Shingo Oda, Ryoichi Fujiwara, Yuki Kutsuno, Tatsuki Fukami, Tomoo Itoh, Tsuyoshi Yokoi, and Miki Nakajima. Targeted screen for human UDP-glucuronosyltransferases inhibitors and the evaluation of potential drug-drug interactions with zafirlukast. Drug Metab. Dispos., 43: 812-818 (2015).

 

7) Masataka Nakano, Yasunari Fukushima, Shin-ichi Yokota, Tatsuki Fukami, Masataka Takamiya, Yasuhiro Aoki, Tsuyoshi Yokoi, and Miki Nakajima. CYP2A7 pseudogene transcript affects CYP2A6 expression in human liver by acting as a decoy for miR-126*. Drug Metab. Dispos., 43: 703-712 (2015).

 

8) Shohei Takai, Shingo Oda, Koichi Tsuneyama, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. Establishment of a mouse model for amiodarone-induced liver injury and analyses of its hepatotoxic mechanismJ. Appl. Toxicol., in press.

 

9) Yun-Ping Lim, Ching-Hao Chen, Wei-Cheng Chen, Shih-Yu Chang, Dong-Zong Hung, Jih-Jung Chen, Lei Wan, Wei-Chih Ma, Yu-Hsien Lin, Cing-Yu Chen, Tsuyoshi Yokoi, Miki Nakajima and Chao-Jung Chen. Allyl isothiocyanate (AITC) inhibits pregnane X receptor (PXR) and constitutive androstane receptor (CAR) activation and protects against acetaminophen- and amiodarone-induced cytotoxicity. Arch. Toxicol., 89: 57-72 (2015).

 

10) Shohei Takai, Satonori Higuchi, Azusa Yano, Koichi Tsuneyama, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. Involvement of immune- and inflammatory-related factors in flucloxacillin-induced liver injury in mice. J. Appl. Toxicol., 35: 142–151 (2015).

総説・著書

1) Shingo Oda and Tsuyoshi Yokoi. Establishment of Animal Models of Drug-induced Liver Injury and Analysis of Possible Mechanisms. Yakugaku Zasshi,  135: 579-588 (2015).

 

2) Shingo Oda*, Tatsuki Fukami*, Tsuyoshi Yokoi, and Miki Nakajima (*Equally contributed). A comprehensive review of UDP-glucuronosyltransferase and esterases for drug development. Drug Metab. Pharmacokinet., 30: 30-51 (2015).

 

 

2014

原著論文

1) Yusuke Ito, Tatsuki Fukami, Tsuyoshi Yokoi, and Miki Nakajima. An orphan esterase ABHD10 mudolates probenecid acyl glucuronidation in human liver. Drug Metab. Dispos., 42: 2109-2116 (2014).

 

2) Eita Sasaki, Atsushi Iwamura, Koichi Tsuneyama, Tatsuki Fukami, Miki Nakajima, Toshiyuki Kume and Tsuyoshi Yokoi. Role of P450-mediated metabolism and identification of novel thiol-conjugated metabolites in mice with phenytoin-induced liver injury. Toxicol. Lett., 232: 79-88 (2014).

 

3) Yun-Ping Lim, Wei-Cheng Chen, Ching-Hao Cheng, Wei-Chih Ma, Yu-Hsien Lin, Cing-Yu Chen, Dong-Zong Hung, Jih-Jung Chen, Tsuyoshi Yokoi, Miki Nakajima, and Chao-Jung Chen. Inhibition of cytochrome P450 2C9 expression and activity in vitro by allyl isothiocyanate. Planta Med., 80: 1097-1106 (2014).

 

4) Mark J. Kurth, Tsuyoshi Yokoi, and M. Eric Gershwin. Halothane-induced hepatitis: Paradigm or paradox for drug-induced liver injury. Hepatology, 60: 1473-1475 (2014).

 

5) Yu Yamaura, Miki Nakajima, Naoyuki Tatsumi, Shingo Takagi, Tatsuki Fukami, Koichi Tsuneyama, and Tsuyoshi Yokoi. Changes in the expression of miRNAs at the pericentral and periportal regions of the rat liver in response to hepatocellular injury: Comparison with the changes in the expression of plasma miRNAs. Toxicology, 322: 89-98 (2014).

 

6) Yuki Oda, Miki Nakajima, Koichi Tsuneyama, Masataka Takamiya, Yasuhiro Aoki, Tatsuki Fukami, and Tsuyoshi Yokoi. Retinoid X receptor alpha in human liver is regulated by miR-34a. Biochem. Pharmacol., 90: 179-187 (2014).

 

7) Mai Shimizu, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. Screening of specific inhibitors for human carboxylesterases or arylacetamide deacetylase. Drug Metab. Dispos., 42: 1103-1109 (2014).

 

8) Azusa Yano, Shingo Oda, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. Development of a cell-based assay system considering drug metabolism and immune- and inflammatory-related factors for the risk assessment of drug-induced liver injury. Toxicol. Lett., 228: 13-24 (2014).

 

9) Seng Chuan Tang, Rolf W. Sparidans, Ka Lei Cheung, Tatsuki Fukami, Selvi Durmus, Els Wagenaar, Tsuyoshi Yokoi, Bart J. M. van Vlijmen, Jos H. Beijnen, and Alfred H. Schinkel. P-glycoprotein, CYP3A and plasma carboxylesterase determine brain and blood disposition of the mTOR inhibitor everolimus (Afinitor) in mice. Clin. Cancer Res., 20: 3133-3145 (2014).

 

10) Shinya Endo, Azusa Yano, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. Involvement of miRNAs in the early phase of halothane-induced liver injury. Toxicology, 319: 75-84 (2014).

 

11) Kei Takahashi, Naoyuki Tatsumi, Tatsuki Fukami, Tsuyoshi Yokoi, and Miki Nakajima. Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab. Pharmacokinet., 29:333-340 (2014).

 

12) Mai Shimizu, Tatsuki Fukami, Yusuke Ito, Takaya Kurokawa, Motoki Kariya, Miki Nakajima, and Tsuyoshi Yokoi. Indiplon is hydrolyzed by arylacetamide deacetylase in human liver. Drug Metab. Dispos., 42: 751-758 (2014).

 

13) Shingo Oda, Tatsuki Fukami, Tsuyoshi Yokoi, and Miki Nakajima. Epigenetic regulation of the tissue-specific expression of human UDP-glucuronosyltransferase (UGT) 1A10. Biochem. Pharmacol., 87: 660-667 (2014).

 

14) Shuichi Kuno, Fuminori Sakurai, Kahori Shimizu, Naoya Matsumura, Soonih Kim, Hitoshi Watanabe, Katsuhisa Tashiro, Masashi Tachibana, Tsuyoshi Yokoi, and Hiroyuki Mizuguchi. Development of mice exhibiting hepatic microsomal activity of human CYP3A4 comparable to that in human liver microsomes by intravenous administration of an adenovirus vector expressing human CYP3A4Drug Metab. Pharmacokinet., 29: 296-304 (2014).

 

15) Kentaro Matsuo, Eita Sasaki, Satorori Higuchi, Shohei Takai, Koichi Tsuneyama, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. Involvement of oxidative stress and immune- and inframmation-related factors in azathioprine-induced liver injury. Toxicol. Lett, 224: 215-224(2014).

 

16) Kyotaka Muta, Tatsuki Muta, Miki Nakajima, and Tsuyoshi Yokoi. N-Glycosylation during translation is essential for human arylacetamide deacetylase enzyme activity. Biochem. Pharmacol., 87: 352-359 (2014).

 

17) Taishi Miyashita, Kento Kimura, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. Evaluation and mechanistic analysis of the cytotoxicity of the acyl glucuronide of nonsteroidal anti-inflammatory drugs. Drug Metab. Dispos., 42: 1-8 (2014).

 

18) Kei Takahashi, Yuki Oda, Yasuyuki Toyoda, Tatsuki Fukami, Tsuyoshi Yokoi, and Miki Nakajima. Regulation of cytochrome b5 expression by miR-223 in human liver; effects on cytochrome P450 activities. Pharm. Res., 31: 780-794 (2014).

 

総説・著書

1) 織田進吾, 横井 毅. 薬物性肝障害における免疫・炎症因子の関与日本皮膚アレルギー・接触皮膚炎学会雑誌, 8: 239-248 (2014).

 

2) 横井 毅肝障害とバイオマーカーとしてのmiRNA谷本学校 毒性質問箱, 16:56-67 (2014).

 

3) 横井 毅薬物代謝と肝障害:薬物代謝と免疫・炎症を考慮した薬物性肝障害の理解と展望. 日本薬理学雑誌, 144: 22-27 (2014).

 

4) 横井 毅薬物代謝と肝障害月刊薬事 56: 21-25 (2014).

 

5) Miki Nakajima and Tsuyoshi Yokoi. MicroRNA-Regulation of P450 and Pharmacogenetics. 「Handbook Pharmacogenomics and Straified Medicines」 Sandosh Padmanabhan Ed. Elsevier, Watham pp.385-401 (2014).

2013

原著論文

1) Eita Sasaki, Kentaro Matsuo, Azumi Iida, Koichi Tsuneyama, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. A novel mouse model for phenytoin-induced liver injury: involvement of immune-related factors and P450-mediated metabolism. Toxicol. Sci., 136:250-263 (2013).

 

2) Kei Takahashi, Shin-ichi Yokota, Naoyuki Tatsumi, Tatsuki Fukami, Tsuyoshi Yokoi, and Miki Nakajima. Cigarette smoking substantially alters plasma microRNA profiles in healthy subjects. Toxicol. Appl. Pharmacol., 272: 154-160 (2013).

 

3) Yukiko Kato, Takeshi Izukawa, Shingo Oda, Tatsuki Fukami, Moshe Finel, Tsuyoshi Yokoi, and Miki Nakajima. Human UGT2B10 in drug N-glucuronidations: substrate screening and comparison with UGT1A3 and UGT1A4. Drug Metab. Dispos., 41: 1389-1397 (2013).

 

4) Ryota Higuchi, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. Prilocaine- and lidocaine-induced methemoglobinemia is caused by human carbosylesterase-, CYP2E1- and CYP3A4-medicated metabolic activation. Drug Metab. Dispos., 41: 1220-1230 (2013).

 

5) Shingo Oda, Tatsuki Fukami, Tsuyoshi Yokoi, and Miki Nakajima. Epigenetic regulation is a crucial factor in the repression of UGT1A1 expression in the human kidney. Drug Metab. Dispos., 41: 1738-1743 (2013).

 

6) Ching Ho Poon, Tsz Yan Wong, Yanfei Wang, Yuki Tsuchiya, Miki Nakajima, Tsuyoshi Yokoi, and Lai K. Leung. The citrus flavanon naringenin suppresses CYP1B1 transactivation through antagonizing xenobiotic-responsive element binding. Br. J. Nutr., 109: 1598-1605 (2013).

 

7) Makoto Kataoka, Yuki Terashima, Katsuhiko Miuno, Yoshie Masaoka, Shinji Saluma, Tsuyoshi Yokoi, and Shinji Yamashita. Establishment of MDCKII cell monolayer with metabolic activity by CYP3A4 transduced with recombinant adnovirus. Drug Metab. Pharmacokinet., 28: 125-131 (2013).

 

総説・著書

1) Tsuyoshi Yokoi. A new era in the study of individual differences in drug metabolism and pharmacokinetics. Drug Metab. Pharmacokinet., 28: 1-2 (2013).

 

2) Tsuyoshi Yokoi and Miki Nakajima. MicroRNAs as mediators of drug toxicity. Ann. Rev. Pharmacol. Toxicol., 53: 377-400 (2013).

 

3) Tatsuki Fukami and Tsuyoshi Yokoi. The Emerging role of human esterases. Drug Metab. Pharmacokinet., 27: 466-477 (2013).

 

4) 横井 毅体内動態と薬物相互作用の基礎と応用-食品成分への展開-.食品加工技術 33: 7-13(2013).

 

5) 横井 毅. 薬物代謝反応・代謝酵素の多様性と薬物相互作用の予測 p198-204. 「In vitro毒性・動態評価の最前線」小島肇監修、シーエムシー出版 (2013).

2012

原著論文

1) Yuki Kobayashi, Tatsuki Fukami, Ryota Higuchi, Miki Nakajima, and Tsuyoshi Yokoi. Metabolic activation by human arylacetamide deacetylase, CYP2E1, and CYP1A2 causes phenacetin-induced methemoglobinemia. Biochem. Pharmacol., 84: 1196-1206 (2012).

 

2) Masakazu Kakuni, Mayu Morita, Kentaro Matsuo, Yumiko Katoh, Miki Nakajima, Chise Tateno, and Tsuyoshi Yokoi. Chimeric mice with a humanized liver as an animal model of troglitazone-induced liver injury. Toxicol. Lett., 214: 9-18 (2012).

 

3) Satonori Higuchi, Azusa Yano, Shohei Takai, Koichi Tsuneyama, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. Metabolic activation and inflammation reactions involved in carbamazepine-induced liver injury. Toxicol. Sci., 130: 4-16 (2012).

 

4) Taisha Miyashita, Yasuyuki Toyoda, Koichi Tsuneyama, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. Hepatoprotecitve effect of tamoxifen on steatosis and non-alcoholic steatohepatitis in mouse models. J. Toxicol. Sci., 37: 931-942 (2012).

 

5) Yukitaka Yoshikawa, Taishi Miyashita, Satorori Higuchi, Koichi Tsuneyama, Shinya Endo, Yasuyuki Toyoda, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. Mechanisms of the hepatoprotective effects of tamoxifen against drug-induced and chemical-induced acute liver injuries. Toxcol. Appl. Pharmacol., 264: 42-50 (2012).

 

6) Shingo Oda, Miki Nakajima, Masahiko Hatakeyama, Tatsuki Fukami, and Tsuyoshi Yokoi. Preparation of a specific monoclonal antibody against human UGT1A9 and evaluation of UGT1A9 protein levels in human tissues. Drug Metab. Dispos., 40: 1620-1627 (2012).

 

7) Shinya Endo, Yasuyuki Toyoda, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. Activation of human monocytic THP-1 cells by metabolic activation of hepatotoxic drugs. Drug Metab. Pharmacokinet., 27: 621-630 (2012).

 

8) Yuki Kobayashi, Tatsuki Fukami, Mai Shimizu, Miki Nakajima, and Tsuyoshi Yokoi. Contributions of arylacetamide deacetylase and carboxylesterase 2 to flutamide hydrolysis in human liver. Drug Metab. Dispos., 40: 1080-1084 (2012).

 

9) Mai Shimizu, Tatsuki Fukami, Yuki Kobayashi, Masataka Takamiya, Yoshihiro Aoki, Miki Nakajima and Tsuyoshi Yokoi. A novel polymorphic allele of human arylacetamide deacetylase leads to diminished enzyme activity. Drug Metab. Dispos., 40: 1183-1190 (2012).

 

10) Kornphimol Kulthong, Rawiwan Maniratanachote, Yuki Kobayashi, Tatsuki Fukami and Tsuyoshi Yokoi. Effects of silver nanoparticles on hepatic cytochrome P450 enzyme activity. Xenobiotica, 42: 854-862 (2012).

 

11) Yuki Oda, Miki Nakajima, Takuya Mohri, Masataka Takamiya, Yasuhiro Aoki, Tatsuki Fukami, and Tsuyoshi Yokoi. Aryl hydrocarbon receptor nuclear translocator in human liver is regulated by miR-24. Toxcol. Appl. Pharmacol., 260: 222-231 (2012).

 

12) Atsushi Iwamura, Tatsuki Fukami, Ryota Higuchi, Miki Nakajima, and Tsuyoshi Yokoi. Human a/b hydrolase domain containing 10 (ABHD10) is a responsible enzyme for deglucuronidation of mycophenolic acid acyl-glucuronide in liver. J. Biol. Chem., 287: 9240-9249 (2012).

 

13) Azusa Yano, Satonori Higuchi, Koichi Tsuneyama, Tasuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. Involvement of immune-related factors in diclofenac-induced acute liver in mice. Toxicology, 293: 107-114 (2012).

 

14) Theerada Taesotikul, Miki Nakajima, Wichittra Tassaneeyakul, and Tsuyoshi Yokoi. Effects of Phyllanthus amarus extract on the pharmacokinetics of midazolam and cytochrome P450 activities in rats. Xenobiotica., 42: 641-648 (2012).

 

15) Masanori Kobayashi, Satorori Higuchi, Mika Ide, Satomi Nishikawa, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. Th2 cytokines-mediated methimazole-induced liver injury in mice. J. Appl. Toxicol., 32: 823-833 (2012).

 

16) Yuki Kobayashi, Tatsuki Fukami, Akinori Nakajima, Akinobu Watanabe, Miki Nakajima, and Tsuyoshi Yokoi. Species differences in tissue distribution and enzyme activities of arylacetamide deacetylase in human, rat, and mouse. Drug Metab. Dispos., 40: 671-679 (2012).

 

17) Yu Yamaura, Miki Nakajima, Shingo Takagi, Tatsuki Fukami, Koichi Tsuneyama, and Tsuyoshi Yokoi. Plasma microRNA profiles in rat models of hepatocellular injury, cholestasis, and steatosis. PLoS One, 7: e30250 (2012).

 

18) Yasuyuki Toyoda, Shinya Endo, Koichi Tsuneyama, Taishi Miyashita, Azusa Yano, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. Mechanism of exacebrative effect of progesterone on drug-induced liver injury. Toxcol. Sci., 126: 16-27 (2012).

 

19) Yukiko Kato, Miki Nakajima, Shingo Oda, Tasuki Fukami, and Tsuyoshi Yokoi. Human UDP-glucuronosyltransferase isoforms involved in haloperidol glucuronidation and quantitative estimation of their contributions. Drug Metab. Dispos., 40: 240-248 (2012).

 

20) Satonori Higuchi, Masanori Kobayashi, Azusa Yano, Koichi Tsuneyama, Tastuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. Involvement of Th2 cytokines in the mouse model of flutamide-induced acute liver injury. J. Appl. Toxicol., 32: 815-822 (2012).

2011

原著論文

1) Shingo Oda, Miki Nakajima, Yasuyuki Toyoda, Tatsuki Fukami, and Tsuyoshi Yokoi. Progesterone receptor membrane component 1 modulates human cytochrome P450 activities in an isoform-dependent manner. Drug Metab. Dispos., 39: 2057-2065 (2011).

 

2) Akinori Nakajima, Tatsuki Fukami, Yuki Kobayashi, Akinobu Watanabe, Miki Nakajima, and Tsuyoshi Yokoi. Human arylacetamide deacetylase is responsible for deacetylation of refamycins: rifampicin, rifabutin, and rifapentine. Biochem. Pharmacol., 82: 1747-1756 (2011).

 

3) Katsuhiko Kida, Miki Nakajima, Takuya Mohri, Yuki Oda, Shingo Takagi, Tasuki Fukami, and Tsuyoshi Yokoi. Peroxisome proliferator-activator receptor a is regulated by miR-21 and miR-27b in human liver. Pharm. Res., 28: 2467-2476 (2011).

 

4) Hiroko Hosomi, Tatsuki Fukami, Atsushi Iwamura, Miki Nakajima, and Tsuyoshi Yokoi. Development of a higyly sensitive cytotoxicity assay system for CYP3A4-mediated metabolic activation. Drug Metab. Dispos., 39: 1388-1395 (2011).

 

5) Tomomi Hioki, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. Human paraoxonase 1 is the enzyme responsible for pilocarpine hydrolysis. Drug Metab. Dispos., 39: 1345-1352 (2011).

 

6) Toru Usui, Takanori Hashizume, Takashi Katsumata, Tsuyoshi Yokoi, and Setsuko Komuro. In vitro investigation of the glutathione transferase M1 and T1 null genotypes as risk factors for troglitazone-induced liver injury. Drug Metab. Dispos., 39: 1303-1310 (2011).

 

7) Yasuyuki Toyoda, Taishi Miyashita, Shinya Endo, Koichi Tsuneyama, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. Estradiol and progesterone modulate halothane-induced liver injury in mice. Toxicol. Lett., 204: 17-24 (2011).

 

8) Atsushi Iwamura, Tatsuki Fukami, Hiroko Hosomi, Miki Nakajima, and Tsuyoshi Yokoi. CYP2C9-mediated metabolic activation of losartan detected by a high sensitive cell-based screening assay. Drug Metab. Dispos., 39: 838-846 (2011).

 

9) Yuko Abe, Ryoichi Fujiwara, Shingo Oda, and Tsuyoshi Yokoi, and Miki Nakajima. Interpretation for the effects of protein kinase C inhibitors on human UDP-glucuronosyltransferase 1A (UGT1A) proteins in cellulo. Drug Metab. Pharmacokinet., 26: 256-265 (2011).

 

10) Satonori Higuchi, Masanori Kobayashi, Yukitaka Yoshikawa, Koichi Tsuneyama, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. IL-4 mediated dicloxacillin-induced liver injury in mice. Toxicol. Lett., 200: 139-145 (2011).

 

11) Toshihisa Koga, Ryoichi Fujiwara, Miki Nakajima, and Tsuyoshi Yokoi. Toxicological evaluation of acyl glucuronides of NSAIDs using HEK293 cells stably expressing human UGT and human hepatocytes. Drug Metab. Dispos., 39: 54-60 (2011).

 

12) Shin-ichi Yokota, Eriko Higashi, Tatsuki Fukami, Tsuyoshi Yokoi, and Miki Nakajima. Human CYP2A6 is regulated by nuclear factor-erythroid 2 related factor 2. Biochem. Pharmacol., 81: 289-294 (2011).

 

13) Katsuhiko Mizuno, Yasuyuki Toyoda, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. Stimulation of pro-inflammatory responses by mebendazole in human monocytic THP-1 cells through an ERK signaling pathwey. Arch. Toxicol., 85: 199-207 (2011).

 

総説・著書

1) Tsuyoshi Yokoi and Miki Nakajima. Toxicological implications of modulation of gene expression by microRNAs. Toxicol. Sci., 123: 1-14 (2011).

 

2) Tsuyoshi Yokoi. Current topics in drug metabolism and drug toxicity. Drug Metab. Pharmacokinet., 26: 1-2 (2011).

 

3) Miki Nakajima and Tsuyoshi Yokoi. MicroRNAs from biology to future pharmacotherapy: regulation of cytochrome P450s and nuclear receptors. Pharmacol. Ther., 131: 330-337 (2011).

 

4) 横井 毅. 第II相代謝の評価と創薬 p224-231.「医薬品開発に必要なストラテジーと各種試験法」日本薬理学会編 (2011).

2010

原著論文

1) Akinobu Watanabe, Tatsuki Fukami, Shiori Takahashi, Nao Nakagawa, Miki Nakajima, and Tsuyoshi Yokoi. Arylacetamide deacethylase is a determinant enzyme for the difference in bydrolase activities of phenacetin and acetaminophen. Drug Metab. Dispos., 38: 1532-1537 (2010).

 

2) Masanori Kobayashi, Satorori Higuchi, Katsuhiko Mizuno, Koichi Tsuneyama, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. Interleukin-17 is involved in a-naphthylisothiocyanate-induced liver injury in mice. Toxicology, 275: 50-57 (2010).

 

3) Tatsuki Fukami, Miki Nakajima, Isao Matsumoto, Yoh Zen, Makoto Oda, and Tsuyoshi Yokoi. Immunohistochemical analysis of CYP2A13 in various types of human lung cancers. Cancer Sci., 101: 1024-1028 (2010).

 

4) Tatsuki Fukami, Shiori Takahashi, Nao Nakagawa, Taiga Maruichi, Miki Nakajima, and Tsuyoshi Yokoi. In vitro evaluation of inhibitory effects of antidiabetic and antihyprelipidemic drugs on human carboxylesterase activities. Drug Metab. Dispos., 38: 2173-2178 (2010).

 

5) Katsuhiko Mizuno, Tatsuki Fukami, Yasuyuki Toyoda, Miki Nakajima, and Tsuyoshi Yokoi. Terbinafine stimulates the pro-nflammatory responses in human monocytic THP-1 cells through an ERK signaling pathwey. Life Sci., 87: 537-544 (2010).

 

6) Roger S Holmes, Matthew Wright, Stanley JF Laulederkind, Laura A Cox, Masakiyo Hosokawa, Teruko Imai, Shun Ishibashi, Richard Lehner Masao Miyazaki, Everett J Perkins, Phillip M Potter, Matthew Redinbo, Jacques Robert, Tetsuo Satoh, Tetsuro Yamashita, Bingfang Yan, Tsuyoshi Yokoi, Rudolf Zechner and Lois Maltais. Recommended nomenclature for five mammalian carboxylesterase gene families: human, mouse and rat genes and proteins. Mammalian Genome, 21: 427-441 (2010).

 

7) Shingo Takagi, Miki Nakajima, Katsuhiko Kida, Yu Yamaura, Tatsuki Fukami, and Tsuyoshi Yokoi. MicroRNAs regulate human hepatocytes nuclear factor 4a modulating the expression of metabolic enzymes and cell cycle. J. Biol. Chem., 285: 4415-4422 (2010).

 

8) Hiroko Hosomi, Sho Akai, Keiichi Minami, Yukitaka Yoshikawa, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. An in vivo drug-induced hepatotoxicity screeing system using CYP3A4-expressing and g-glutamylcysteine synthetase knockdown cells. Toxicol. in Vitro, 24: 1032-1038 (2010).

 

9) Miki Nakajima, Toshihisa Koga, Haruko Sakai, Hiroyuki Yamanaka, Ryoichi Fujiwara, and Tsuyoshi Yokoi. N-Glycosylation plays a role in protein folding to human UGT1A9. Biochem. Pharmacol., 79: 1165-1172 (2010).

 

10) Takuya Mohri, Miki Nakajima, Tatsuki Fukami, Masataka Takamiya, Yasuhiro Aoki, and Tsuyoshi Yokoi. Human CYP2E1 is regulated by miR-378. Biochem. Pharmacol., 79: 1045-1052 (2010).

 

11) Taiga Maruichi, Tatsuki Fukami, Miki Nakajima, and Tsuyoshi Yokoi. Transcriptional regulation of human carboxylesterase 1A1 by nuclear factor ?erythroid 2 related factor 2 (Nrf2). Biochem. Pharmacol., 79: 288-295 (2010).

 

12) Ryoichi Fujiwara, Miki Nakajima, Shingo Oda, Hiroyuki Yamanaka, Shin-ichi Ikushiro, Toshiyuki Sakaki, and Tsuyoshi Yokoi. Interactions between human UDP-glucuronosyltransferese (UGT) 2B7 and UGT1A enzymes. J. Pharm. Sci., 99: 442-454 (2010).

総説・著書

1) 横井 毅. 薬物動態関連遺伝子の多型と薬物相互作用. 臨床検査 54:1107-1113(2010).

 

2)  横井 毅. 薬物代謝異常と小胞体 p235-250. 「生物薬科学実験講座5、細胞の構造とオルガネラ」大熊勝治、中西義信編集、廣川書店 (2010).

 

3) 横井 毅. 薬物代謝に関与する酵素とその反応機構 p43-68、 薬物代謝と毒性発現 p182-192.「薬物代謝学 医療薬学・医薬品開発の基礎として第3版」加藤隆一、山添 康、横井 毅編、 東京化学同人 (2010).

 

4) Tsuyoshi YokoiTroglitazone p419-435. 「Adverse Drug Reactions」 Jack Uetrecht Ed. in Handbook of Expreimental Pharmacology 196, Springer-Verlag, Berlin (2010).