Kouichi YOSHINARI, Ph.D.
Professor,Department of Molecular Toxicology,
School of Pharmaceutical Sciences, University of Shizuoka,
52-1 Yada, Suruga-ku, Shizuoka 422-8526, JAPAN
Telephone/fax: +81-54-264-5685
E-mail: yoshinari@u-shizuoka-ken.ac.jp
Url: http://w3pharm.u-shizuoka-ken.ac.jp/eisei/Japanese/Top.html
Education
Ph. D., Pharmaceutical Sciences: Tohoku University, Graduate School of Pharmaceutical
Sciences (April 1995-March 1998).
M.S., Pharmaceutical Sciences: Tohoku University, Graduate School of Pharmaceutical
Sciences (April 1993-March 1995).
B.S. Pharmaceutical Sciences: Tohoku University, Faculty of Pharmaceutical Sciences.
(April 1989-March 1993).
Employment
April 2014-present: University of Shizuoka, School of Pharmaceutical Sciences, Professor.
March 2007-March 2014: Tohoku University, Graduate School of Pharmaceutical Sciences,
Associate Professor
April 2006-February 2007: Tohoku University, Graduate School of Pharmaceutical Sciences,
Assistant Professor.
April 2002 – March 2006: University of Shizuoka, School of Pharmaceutical Sciences,Assistant Professor.
October 2001-Mrach 2002: University of Shizuoka, School of Pharmaceutical Sciences,
Research Assistant Professor.
April 1998-September 2001: National Institute of Environmental Health
Sciences/National Institutes of Health, Postdoctoral Fellow.
Research Interests
・ Gene regulation of drug-metabolizing enzymes.
・ Roles of xenobiotic-responsive nuclear receptors in liver function and toxicity.
・ Chemical-induced liver toxicity: the identification of mechanisms and the development ofprediction system.
Academic Honors
2018 The Pharmaceutical Society of Japan Award for Divisional Scientific Promotion
2017 Japanese Society of Toxicology/Japan Chemical Industry Association LRI Award
2011 International Society for the Study of Xenobiotics (ISSX), Asia Pacific New InvestigatorAward
2009 Japanese Society for the Study of Xenobiotics (JSSX), Award for Young Scientists.
2005 The Pharmaceutical Society of Japan, Tokai-region Award for Young Scientists.
List of Publication (Selected)
Books (English)
Receptor-mediated regulation of cytochromes P450. K. Yoshinari, E. Tien, M. Negishi and P.
Honkakoski: in Cytochrome P450: Role in the Metabolism and Toxicity of Drugs andOther Xenobiotics (Issues in Toxicology). C. Ioannides (Edt.), Royal Society of Chemistry.
pp. 417-448, 2008
Review articles

Nuclear receptor CAR-mediated liver cancer and its species differences. R. Shizu, K.
Yoshinari: Expert Opin Drug Metab Toxicol, 16: 343-351, 2020.
Role of nuclear receptors PXR and CAR in xenobiotic-induced hepatocyte proliferation andchemical carcinogenesis. K. Yoshinari: Biol Pharm Bull, 42: 1243-1252, 2019.
Construction of a CYP2E1-template system for prediction of the metabolism on both site andpreference order. Y. Yamazoe, K. Ito, K. Yoshinari: Drug Metab Rev, 43: 409-439, 2011.
Roles of nuclear receptors in the gene expression of drug-metabolizing enzymes undervarious physiological conditions. K. Yoshinari: Yakugakuzasshi, 126: 343-348, 2006.
Original articles
Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury.
Y Shimizu, T Sasaki, E Yonekawa, H Yamazaki, R Ogura, M Watanabe, T Hosaka, RShizu, J. Takeshita, K. Yoshinari: J Toxicol Sci, 2021, in press.
The influence of the long-term chemical activation of the nuclear receptor pregnane X
receptor (PXR) on liver carcinogenesis in mice. R. Shizu, M. Ishimura, S. Nobusawa, T.
Hosaka, T. Sasaki, S. Kakizaki, K. Yoshinari: Arch Toxicol, 95: 1089, 2021.
PXR functionally interacts with NF-κB and AP-1 to downregulate the inflammation-induced
expression of chemokine CXCL2 in mice. M. Okamura, R. Shizu, T. Abe, S. Kodama, T.
Hosaka, T. Sasaki, K. Yoshinari: Cells, 9: 2296, 2020.
Antiepileptic drug-activated constitutive androstane receptor inhibits peroxisome
proliferator-activated receptor α- and peroxisome proliferator-activated receptor γ
coactivator 1α-dependent gene expression to increase blood triglyceride levels. R. Shizu,Y. Otsuka, K. Ezaki, C. Ishii, S. Arakawa, Y. Amaike, T. Abe, T. Hosaka, T. Sasaki, Y.
Kanno, M. Miyata, Y. Yamazoe, K. Yoshinari: Mol Pharmacol, 98: 634-647, 2020.
Enhancement of acetaminophen-induced chronic hepatotoxicity in spontaneously diabetictorii (SDT) rats. K. Kondo, N. Yamada, Y. Suzuki, T. Hashimoto, K. Toyoda, T. Takahashi,
A. Kobayashi, S. Sugai, K. Yoshinari: J Toxicol Sci, 45: 245, 2020.
Construction of a PPARα reporter assay system with drug-metabolizing capability. T. Hosaka,A. Wakatsuki, T. Sasaki, R. Shizu, K. Yoshinari: BPB Reports. 3: 7, 2020.
Application of cytochrome P450 reactivity on the characterization of chemical compounds andits association with repeated-dose toxicity. M. Watanabe, T. Sasaki, J. Takeshita, M.
Kushida, Y. Shimizu, H. Oki, Y. Kitsunai, H. Nakayama, H. Saruhashi, R. Ogura, R. Shizu,
T. Hosaka, K. Yoshinari: Toxicol Appl Pharmacol, 388: 114854, 2020.
Functional interaction between pregnane X receptor and yes-associated protein in
xenobiotic-dependent liver hypertrophy and drug metabolism. T. Abe, R. Shizu, T. Sasaki,Y. Shimizu, T. Hosaka, S. Kodama, A. Matsuzawa, K. Yoshinari: J Pharmacol Exp Ther.
371: 590, 2019.
Possible involvement of the competition for the transcriptional coactivator glucocorticoid
receptor-interacting protein 1 in the inflammatory signal-dependent suppression ofPXR-mediated CYP3A induction in vitro. M. Okamura, R. Shizu, T. Hosaka, T. Sasaki, K.
Yoshinari: Drug Metab Pharmacokinet, 34: 272, 2019.
Chimeric mice with humanized livers demonstrate human-specific hepatotoxicity caused by atherapeutic antibody against TRAIL-receptor 2/death receptor 5. K. Nihira, K. Nan-ya, M.
Kakuni, Y. Ono, Y. Yoshikawa, T. Ota, M. Hiura, K. Yoshinari: Toxicol Sci, 167: 190,2019.
Profiling of bisphenol A and eight its analogues on transcriptional activity via human nuclear
receptors. H. Kojima, S. Takeuchi, S. Sanoh, K. Okuda, S. Kitamura, N. Uramaru, K.
Sugihara, K. Yoshinari: Toxicology, 413: 48, 2019.
Screening of industrial and agricultural chemicals for searching a mouse PXR activator using
cell-based reporter gene assays. R. Shizu, M. Kano, T. Abe, S. Tsuchiy, Y. Shimizu, M.
Watanabe, T. Hosaka, T. Sasaki, K. Yoshinari: BPB Reports, 1, 11, 2018.
Role of YAP activation in nuclear receptor CAR-mediated proliferation of mouse hepatocytes.
T. Abe, Y. Amaike, R. Shizu, M. Takahashi, M. Kano, T. Hosaka, T. Sasaki, S. Kodama, A.
Matsuzawa, K. Yoshinari: Toxicol Sci, 165: 408, 2018.
Acceleration of murine hepatocyte proliferation by imazalil through the activation of nuclear

receptor PXR. S. Yoshimaru, R. Shizu, S. Tsuruta, Y. Amaike, M. Kano, T. Hosaka, T.
Sasaki, K. Yoshinari: J Toxicol Sci, 43: 443, 2018.
Characterization of CYP2C induction in cryopreserved human hepatocytes and its applicationin the prediction of the clinical consequences of the induction. M. Nagai, T. Hosaka, M.
Satsukawa, K. Yoshinari: J Pharm Sci, 107: 2479, 2018.
Discriminative models using molecular descriptors for predicting increased serum ALT levels
in repeated-dose toxicity studies of rats. J. Takeshita, H. Nakayama, Y. Kitsunai, M.
Tanabe, H. Oki, T. Sasaki, K. Yoshinari: Comp Toxicol, 6: 64, 2018.
Pregnenolone 16α-carbonitrile ameliorates concanavalin A-induced liver injury in miceindependent of the nuclear receptor PXR activation. S. Kodama, T. Shimura, H.
Kuribayashi, T. Abe, K. Yoshinari: Toxicol Lett, 271: 58, 2017.
Activation of nuclear receptor CAR by an environmental pollutant perfluorooctanoic acid. T.
Abe, M. Takahashi, M. Kano, Y. Amaike, C. Ishii, K. Maeda, Y. Kudoh, T. Morishita, T.
Hosaka, T. Sasaki, S. Kodama, A. Matsuzawa, H. Kojima, K. Yoshinari: Arch Toxicol, 91:2365, 2017.
Establishment of in silico prediction models for CYP3A4 and CYP2B6 induction in humanhepatocytes by multiple regression analysis using azole compounds. M. Nagai, Y. Konno,
M. Satsukawa, S Yamashita, K. Yoshinari: Drug Metab Dispos, 44: 1390-8, 2016.
PXR stimulates growth factor-mediated hepatocyte proliferation by cross-talk with FOXO
transcription factor. R. Shizu, T. Abe, S. Benoki, M. Takahashi, S. Kodama, M. Miyata, A.
Matsuzawa, K. Yoshinari: Biochem J, 473: 257, 2016.
Dual roles of nuclear receptor liver X receptor a (LXRa) in the CYP3A4 expression in humanhepatocytes as a positive and negative regulator. K. Watanabe, K. Sakurai, Y. Tsuchiya, Y.
Yamazoe, K. Yoshinari. Biochem Pharmacol, 86: 428, 2013.
Novel cell-based reporter assay system using epitope-tagged protein for the identification ofagonistic ligands of constitutive androstane receptor (CAR). J. Imai, Y. Yamazoe, K.
Yoshinari. Drug Metab Pharmacokinet, 28: 290, 2013.
Xenobiotic-induced hepatocyte proliferation associated with constitutive active/androstanereceptor (CAR) or peroxisome proliferator- activated receptor a (PPARa) is enhanced bypregnane X receptor (PXR) activation in mice. R. Shizu, S. Benoki, Y. Numakura, S.
Kodama, M. Miyata, Y. Yamazoe, K. Yoshinari. PLoS One, 8: e61802, 2013.
Constitutive androstane receptor transactivates the hepatic expression of mouse Dhcr24 andhuman DHCR24 encoding a cholesterogenic enzyme 24-dehydrocholesterol reductase.
K. Yoshinari, H. Ohno, S. Benoki, Y. Yamazoe. Toxicol Lett, 208: 185, 2012.
Transactivation of ABCG2 through a novel cis-element in the distal promoter by constitutive
androstane receptor but not pregnane X receptor in human hepatocytes. S. Benoki, K.
Yoshinari, T. Chikada, J. Imai, Y. Yamazoe: Arch Biochem Biophys, 517: 123, 2012.
Liver X receptor alpha bidirectionally transactivates human CYP1A1 and CYP1A2 throughtwo cis-elements common to both genes. K. Araki, K. Watanabe, Y. Yamazoe, K.
Yoshinari: Toxicol Lett, 215: 16, 2012.
Activated sterol regulatory element-binding protein-2 suppresses hepatocyte nuclear
factor-4-mediated Cyp3a11 expression in mouse liver. S. Inoue, K. Yoshinari, M.
Sugawara, Y. Yamazoe: Mol Pharmacol, 79: 148, 2011.
Clioquinol is sulfated by human jejunum cytosol and SULT1A3, a human-specific dopamine
sulfotransferase. K. Yoshinari, M. Sakamoto, L. Senggunprai, Y. Yamazoe: Toxicol Lett,
206: 229, 2011.
Constitutive androstane receptor transcriptionally activates human CYP1A1 and CYP1A2
genes through a common regulatory element in the 5'-flanking region. K. Yoshinari, N.
Yoda, T. Toriyabe and Y. Yamazoe: Biochem Pharmacol, 79: 261-9, 2010.
Simultaneous expression of plural forms of human cytochrome P450 at desired ratios in
HepG2 cells: adenovirus-mediated tool for cytochrome P450 reconstitution. K. Aoyama,K. Yoshinari, H. J. Kim, K. Nagata, Y. Yamazoe: Drug Metab Pharmacokinet, 24: 209,
2009.
Inhibitory effects of kynurenic acid, a tryptophan metabolite, and its derivatives on cytosolic
sulfotransferases.L. Senggunprai, K. Yoshinari, Y. Yamazoe: Biochem J, 422: 455, 2009.

Selective role of sulfotransferase 2A1 (SULT2A1) in the N-sulfoconjugation of quinolone
drugs in humans. L. Senggunprai, K. Yoshinari, Y. Yamazoe: Drug Metab Dispos, 37:
1711, 2009.
Involvement of Vitamin D receptor in the intestinal induction of human ABCB1. S. Tachibana,K. Yoshinari, T. Chikada, T. Toriyabe, K. Nagata, Y. Yamazoe: Drug Metab Dispos, 37:
1604, 2009.
Unveiling a new essential cis element for the transactivation of the CYP3A4 gene byxenobiotics. T. Toriyabe, K. Nagata, T. Takada, Y. Aratsu, T. Matsubara, K. Yoshinari, Y.
Yamazoe: Mol Pharmacol, 75: 677, 2009.
Omeprazole transactivates human CYP1A1 and CYP1A2 expression through the common
regulatory region containing multiple xenobiotic-responsive elements. K. Yoshinari, R.
Ueda, K. Kusano, T. Yoshimura, K. Nagata, Y. Yamazoe: Biochem Pharmacol, 76: 139,
2008.
Involvement of ST1B subfamily of cytosolic sulfotransferase in kynurenine metabolism to form
natriuretic xanthurenic acid sulfate. L. Senggunprai, K. Yoshinari, M. Shimada, Y.
Yamazoe: J Pharmacol Exp Ther, 327: 789, 2008.
Hepatic CYP3A expression is attenuated in obese mice fed a high-fat diet. K. Yoshinari, S.
Takagi, T. Yoshimasa, J. Sugatani, M. Miwa: Pharm Res, 23: 1188, 2006.
Changes in the expression of cytochromes P450 and nuclear receptors in the liver ofgenetically diabetic db/db mice. K. Yoshinari, S. Takagi, J. Sugatani, M. Miwa: Biol
Pharm Bull, 29: 1634, 2006.
Induction of detoxifying enzymes in rodent white adipose tissue by aryl hydrocarbon receptor
agonists and antioxidants. K. Yoshinari, N. Okino, T. Sato, J. Sugatani, M. Miwa: DrugMetab Dispos, 34: 1081, 2006.
Expression and induction of cytochromes P450 in rat white adipose tissue. K. Yoshinari, T.
Sato, N. Okino, J. Sugatani and M. Miwa: J Pharmacol Exp Ther, 311: 147-54, 2004.
Identification of the nuclear receptor CAR:HSP90 complex in mouse liver and recruitment ofprotein phosphatase 2A in response to phenobarbital. K. Yoshinari, K. Kobayashi, R.
Moore, T. Kawamoto, M. Negishi: FEBS Lett, 548: 17, 2003.
Role of constitutive androstane receptor in the in vivo induction of Mrp3 and CYP2B1/2 byphenobarbital. H. Xiong, K. Yoshinari, K.L. Brouwer, M. Negishi: Drug Metab Dispos, 30:918, 2002.
Nuclear receptor CAR as a regulatory factor for the sexually dimorphic induction of CYB2B1gene by phenobarbital in rat livers. K. Yoshinari, T. Sueyoshi, R. Moore, M. Negishi: Mol
Pharmacol, 59: 278, 2001.
The phenobarbital response enhancer module in the human bilirubin UDP-glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR. J. Sugatani, H.
Kojima, A. Ueda, S. Kakizaki, K. Yoshinari, Q. H. Gong, I. S. Owens, M. Negishi, T.
Sueyoshi: Hepatology, 33: 1232, 2001.
Estrogen activation of the nuclear orphan receptor CAR (constitutive active receptor) ininduction of the mouse Cyp2b10 gene. T. Kawamoto, S. Kakizaki, K. Yoshinari, M.
Negishi: Mol Endocrinol, 14: 1897, 2000.
Molecular cloning, expression, and enzymatic characterization of rabbit hydroxysteroid
sulfotransferase AST-RB2 (ST2A8). K. Yoshinari, K. Nagata, T. Shiraga, K. Iwasaki, T.
Hata, M. Ogino, R. Ueda, K. Fujita, M. Shimada, Y. Yamazoe: J Biochem, 123: 740,
1998.
Molecular characterization of ST1C1-related human sulfotransferase. K. Yoshinari, K. Nagata,
M. Shimada, Y. Yamazoe: Carcinogenesis, 19: 951, 1998.
Molecular cloning and expression of an amine sulfotransferase cDNA: a new gene family ofcytosolic sulfotransferases in mammals. K. Yoshinari, K. Nagata, M. Ogino, K. Fujita, T.
Shiraga, K. Iwasaki, T. Hata, Y. Yamazoe: J Biochem, 123: 479, 1998.