CURRICULUM VITAE
Ryota SHIZU, Ph.D.
Assistant Professor,
Laboratory of Molecular Toxicology,
School of Pharmaceutical Sciences, University of Shizuoka.
52-1 Yada, Suruga-ku, Shizuoka, 422-8526 Japan
Telephone: +81-54-264-5680
E-mail: r_shizu@u-shizuoka-ken.ac.jp

Education:
Apr, 2011-Mar, 2014

Graduate School of Pharmaceutical Sciences, Tohoku
University, Sendai, Japan (Ph.D.)

Apr, 2009-Mar, 2011

Graduate School of Pharmaceutical Sciences, Showa
University, Tokyo, Japan (Master)Apr, 2005-Mar, 2009Showa University, Tokyo, Japan

Professional Experience:
Jul, 2023-present

Assistant Professor, Laboratory of Molecular Toxicology,
School of Pharmaceutical Sciences, University of Shizuoka.

Apr, 2017-Jun, 2023

Research Assistant Professor, Laboratory of MolecularToxicology, School of Pharmaceutical Sciences, University ofShizuoka.

Apr, 2014-Mar, 2017

Visiting Fellow, Pharmacogenetics group, Reproductive &Developmental Biology Laboratory Branch, National Instituteof environmental Sciences, NIH, Research Triangle Park, NC,
USA

Research Interests:

Toxicology, Nuclear receptors, Co-activator, transcription
factor,

Genetranscription,

Proteincarcinogenesis, Liver hypertrophy,

interaction,

LiverQualification and skills:March, 2014

Ph. D (Pharm.D., Tohoku University)May, 2009Japanese pharmacist

Publications:1.

Shizu R, Otsuka Y, Ishii C, Ezaki K, Yoshinari K, PPARα induces the expression of CAR
that works as a negative regulator of PPARα functions in mouse livers, Int J Mol Sci,24, 3953, 2023

2.

Watanabe M, Kosaka H, Sugawara M, Maemoto M, Ono Y, Uemori T, Shizu R, Yoshinari
K, Screening for DAX1/EWS-FLI1 functional inhibitors identified dihydroorotate
dehydrogenase as a therapeutic target for Ewing’s sarcoma, Cancer Med, 12, 98029814, 2023

3.

Murase W, Kubota A, Ikeda-Araki M, Terasaki K Nakagawa K, Shizu R, Yoshinari K,Kojima H, Effects of perfluorooctanoic acid (PFOA) on gene expression profiles via
nuclear receptors in HepaRG cells: Comparative study with in vitro transactivation
assays, Toxicology, 153577, 2023

4.

Sato T, Shizu R, Miura Y, Hosaka T, Kanno Y, Sasaki T, Yoshinari K, Developmentof a strategy to identify and evaluate direct and indirect activators of constitutive
androstane receptor in rats. Food Chem Toxicol, 170, 113510, 2022

5.

Kanno Y, Saito N, Yamashita N, Ota K, Shizu R, Hosaka T, Nemoto K, Yoshinari K,
Possible involvement of the upregulation of ΔNp63 expression mediated by HER2activated aryl hydrocarbon receptor in mammosphere maintenance. Int J Mol Sci, 23,12095, 2022

6.

Kanno Y, Saito N, Saito R, Kosuge T, Shizu R, Yatsu T, Hosaka T, Nemoto K, Kato K,
Yoshinari K, Differential DNA-binding and cofactor recruitment are possible determinantsof the synthetic steroid YK11-dependent gene expression by androgen receptor in breast
cancer MDA-MB 453 cells. Exp Cell Res, 419, 113333, 2022

7.
8.

9.

Shizu R, Nishiguchi H, Tashiro S, Sato T, Sugawara A, Kanno Y, Hosaka T, Sasaki T,Yoshinari K, Structural characterization of constitutive transcriptional activity of thenuclear receptor pregnane X receptor (PXR) to generate ligand-sensitive PXR mutantsfor chemical screening. J Biol Chem, 297, 100978, 2021
Shizu R, Ishimura M, Nobusawa S, Hosaka T, Sasaki T, Kakizaki S, Yoshinari K, The
influence of the long-term chemical activation of the nuclear receptor pregnane Xreceptor (PXR) on liver carcinogenesis in mice. Arch Toxicol, 95, 1089-1102, 2021

10. Shizu R, Ezaki K, Sato T, Sugawara A, Hosaka T, Sasaki T, Yoshinari K, PXR
suppresses PPARα-dependent HMGCS2 gene transcription through inhibiting theinteraction between PPARα and PGC1α. Cells, 10, 3550, 2021
11. Lee SJ, Shizu R, Negishi M, Glucocorticoid receptor dimerization in the cytoplasm mightbe essential for nuclear localization. Biochem Biophys Res Commun, 553, 154-159,2021
12. Shimizu Y, Sasaki T, Takeshita J, Watanabe M, Shizu R, Hosaka T, Yoshinari K, Averagemolecular weight as a useful chemical descriptor to discriminate liver injury-inducingdrugs. PLoS One, 16, e0253855, 2021
13. Shimizu Y, Sasaki T, Yonekawa E, Yamazaki H, Ogura R, Watanabe M, Hosaka T, Shizu
R, Takeshita J, Yoshinari K, Association of CYP1A1 and CYP1B1 inhibition with druginduced liver injury. J Toxicol Sci, 46, 167-176, 2021
14. Asai T, Takeshita J, Shimizu Y, Tochikubo Y, Shizu R, Hosaka T, Kanno Y, Yoshinari
K,Chemical characterization of anemia-inducing aniline-related substances and theirapplication to the construction of a decision tree-based anemia prediction model, Food
Chem Toxicol, 157, 12548, 2021
15. Shizu R, Otsuka Y, Ezaki K, Ishii C, Arakawa S, Amaike Y, Abe T, Hosaka T, Sasaki T,Kanno Y, Miyata M, Yamazoe Y, Yoshinari K, Antiepileptic drug-activated constitutive
androstane receptor inhibits peroxisome proliferator-activated receptor α- andperoxisome proliferator-activated receptor γ coactivator 1α-dependent gene expression
to increase blood triglyceride levels. Mol Pharmacol, 98, 634-647, 2020
16. Okamura M, Shizu R, Abe T, Kodama S, Hosaka T, Sasaki T, Yoshinari K, PXR
functionally interacts with NF-κB and AP-1 to downregulate the inflammation-induced
expression of chemokine CXCL2 in mice. Cells, 9, 2296, 2020
17. Hosaka T, Wakatsuki A, Sasaki T, Shizu R, Yoshinari K, Construction of a PPARαreporter assay system with drug-metabolizing capability. BPB Reports, 3, 7-10, 2020
18. Watanabe M, Sasaki T, Takeshita J, Kushida M, Shimizu Y, Oki H, Kitsunai Y, Nakayama
H, Saruhashi H, Ogura R, Shizu R, Hosaka T, Yoshinari K, Application of cytochrome
P450 reactivity on the characterization of chemical compounds and its association withrepeated-dose toxicity. Toxicol Appl Pharmacol, 388, 114854, 2020
19. Shizu R, Yokobori K, Perera L, Pedersen L, Negishi M, Ligand induced dissociationof the AR homodimer precedes AR monomer translocation to the nucleus. Sci Rep,9, 16734, 201920. Abe T, Shizu R, Sasaki T, Shimizu Y, Hosaka T, Kodama S, Matsuzawa A, YoshinariK, Functional interaction between PXR and YAP in xenobiotic-dependent liver
hypertrophy and drug metabolism. J Pharmacol Exp Ther, 371, 590-601, 201921. Okamura M, Shizu R, Hosaka T, Sasaki T, Yoshinari K, Possible involvement of thecompetition for the transcriptional coactivator glucocorticoid receptor-interacting
protein 1 in the inflammatory signal-dependent suppression of PXR-mediated
CYP3A induction in vitro. Drug Metab Pharmacokinet, 34, 272-279, 2019

22. Shizu R, Kano M, Abe T, Tsuchiya S, Shimizu Y, Watanabe M, Hosaka T, Sasaki T,Yoshinari K, Screening of industrial and agricultural chemicals for searching a mouse
PXR activator using cell-based reporter gene assays. BPB Reports, 1, 11-19, 2018.
23. Yoshimaru S, Shizu R, Tsuruta S, Amaike Y, Kano M, Hosaka T, Sasaki T, Yoshinari
K, Acceleration of murine hepatocyte proliferation by imazalil through the activationof nuclear receptor PXR. J Toxicol Sci, 43, 443-450, 2018.
24. Abe T, Amaike Y, Shizu R, Takahashi M, Kano M, Hosaka T, Sasaki T, Kodama S,Matsuzawa A, Yoshinari K, Role of YAP activation in nuclear receptor CAR-mediatedproliferation of mouse hepatocytes. Toxicol Sci, 165, 408-419, 201825. Shizu R, Min J, Sobhany M, Pedersen LC, Mutoh S, Negishi M, Interaction of thephosphorylated DNA-binding domain in nuclear receptor CAR with its ligand binding
domain regulates CAR activation. J Biol Chem, 293, 333-344, 2018.
26. Shizu R, Osabe M, Perera L, Moore R, Sueyoshi T, Negishi M, Phosphorylated
nuclear receptor CAR forms a homodimer to repress its constitutive activity for ligand
activation. Mol Cell Biol, 37, e00649-16, 2017.
27. Shizu R, Abe T, Benoki S, Takahashi M, Kodama S, Miyata M, Matsuzawa A,Yoshinari K, PXR stimulates growth factor-mediated hepatocyte proliferation bycross-talk with FOXO transcription factor. Biochem J, 473, 257-266, 2015.
28. Shizu R, Benoki S, Numakura Y, Kodama S, Miyata M, Yamazoe Y, Yoshinari K,
Xenobiotic-induced hepatocyte proliferation associated with constitutive
active/androstane receptor (CAR) or peroxisome proliferator-activated receptor α(PPARα) is enhanced by pregnane X receptor (PXR) activation in mice. PLoS One,8, e6180, 2013.
29. Shizu R, Shindo S, Yoshida T, Numazawa S, Cross-talk between constitutive
androstane receptor and hypoxia-inducible factor in the regulation of gene
expression. Toxicology Letters, 219, 143-150, 2013.
30. Shizu R, Shindo S, Yoshida T, Numazawa S, MicroRNA-122 down-regulation is
involved in phenobarbital-mediated activation of the constitutive androstane receptor.
PLoS One, 7, e41291, 2012.

Reviews and book chapters:
1.

Shindo S, Kakizaki S, Sakaki T, Kawasaki Y, Sakuma T, Negishi M, Shizu R,
Phosphorylation of Nuclear Receptors: Novelty and Therapeutic Implications,Pharm Ther, 248, 108477, 2023

2.

Shizu R, Understanding the underlying mechanism of xenobiotic-sensing nuclear
recepeptor activation. Yakugaku Zasshi, in press, 2023.

3.

Yoshinari K, Shizu R, Distinct roles of the sister nuclear receptors PXR and CAR inliver cancer development. Drug Metab Dispos, 2022

4.

Shizu R, Yoshinari K, Nuclear receptor CAR-mediated liver cancer and its speciesdifferences. Expert Opin Drug Metab Toxicol., 16, 343-351, 2020.

5.

Shizu R, Numazawa S, Yoshida T, Involvement of microRNA in the induction of drugmetabolizing enzymes. Yakugaku Zasshi, 132, 311-318, 2012.

Honors:1.

Young Scientist Award, The Japanese Society of Toxicology, 2023

2.

Tanabe award, The Japanese Society of Toxicology, 2023

3.

Young Scientist Award, Tokai Branch, The Pharmaceutical Society of Japan, 2023

4.

Young Poster Award, 80th Japanese Cancer Association Annual Meeting, 2021

5.

Postdoctoral poster award, The 12th international ISSX meeting, Portland, OR,
2019

6.

Tanabe award, The Japanese Society of Toxicology, 20197.

Best poster award, The 21st International symposium on Microsomes and DrugOxidations, Davis, CA, 2016

8.

Travel grant, Gordon Research Conference (Drug Metabolism), Holderness, NH,2015