Graduate School of Medicine ＞ Human Sciences
＞ Molecular Pharmacology(Pharmacy)



Professor: Shigeru Ohmori
Associate Professor: Katsunori Nakamura

Summary of Activity
We investigate the expression patterns of Cytochrome P450 (CYP) genes, transcriptional factors, and CYP activity during in vitro differentiation of Embryonic stem (ES) cells into hepatocytes (Fig. 1). While some medications are considered safe to be taken during pregnancy, the effects of other medications on fetus are unknown. Therefore, it is very important to make the model systems which mimic the pregnant woman and fetal liver metabolism. We also interested in the rapid genotyping methods of SNPs in CYPs, FMOs, VKOR, UGTs, GSTs, CESs, Transporters, EGFR, BRAF, and KRAS. (Fig. 2).


Research Projects
We are interested in the molecular and cellular mechanisms of Cytochrome P450 (CYP) gene expression and activity that are responsible for drug metabolism. Current reserches are as follows; 1) CYP gene expression and activity in human fetal membranes and placenta, 2) Differentiation of embryonic stem cells into hepatocytes and mRNA expression of CYP, 3) Formation of large vacuoles induced by cooperative effects of oncostatin M and dexamethasone in human fetal liver cells, 4) Comparison of basal gene expression and induction of CYP3As in HepG2 and fetal liver cells and 5) MDR1 polymorphisms effect cyclosporine AUC0-4 values in Behçet's disease patients.


Fig. 1 Development of new ADME research method by ES cell.


Fig. 2 Rapid genotyping of KRAS mutation by Q-probe method.
References
  1. Maezawa K, Matsunaga T, Takezawa T, Kanai M, Ohira S, Ohmori S. Maezawa K, Matsunaga T, Takezawa T, Kanai M, Ohira S, Ohmori S: Cytochrome P450 3As gene expression and testosterone 6beta-hydroxylase activity in human fetal membranes and placenta at full term. Biochem Pharm Bull 33: 249-254, 2010.

  2. Momose Y, Matsunaga T, Murai K, Takezawa T, Ohmori S: Differentiation of monkey embryonic stem cells into hepatocytes and mRNA expression of cytochrome p450 enzymes responsible for drug metabolism: comparison of embryoid body formation conditions and matrices. Biochem Pharm Bull 32: 619-626, 2009.

  3. Teramoto T, Matsunaga T, Toba M, Sunazuka T, Omura S, Ohmori S: Role of dexamethasone and oncostatin M on the formation of vacuoles in human fetal liver cells. Biochem Pharm Bull 32: 209-212, 2009.

  4. Maezawa K, Miyazato K, Matsunaga T, Momose Y, Imamura T, Johkura K, Sasaki K, Ohmori S: Expression of cytochrome P450 and transcription factors during in vitro differentiation of mouse embryonic stem cells into hepatocytes. Drug Metab Pharmacokinet 23: 188-195, 2008.

  5. Matsunaga T, Toba M, Teramoto T, Mizuya M, Aikawa K, Ohmori S: Formation of large vacuoles induced by cooperative effects of oncostatin M and dexamethasone in human fetal liver cells. Med Mol Morphol 41: 53-58, 2008.

  6. Maruyama M, Matsunaga T, Harada E, Ohmori S: Comparison of basal gene expression and induction of CYP3As in HepG2 and human fetal liver cells. Biochem Pharm Bull 30: 2091-2097, 2007.

  7. Katsuyama Y, Ota M, Mizuki N, Ito A, Okada E, Ohno S, Matsunaga T, Fukushima H, Ohmori S: MDR1 polymorphisms effect cyclosporine AUC0-4 values in Behçet's disease patients. Clin Ophthalmol 1: 297-303, 2007.

  8. Matsunaga T, Kose E, Yasuda S, Ise H, Ikeda U, Ohmori S: Determination of P-glycoprotein ATPase Activity using Luciferase. Biochem Pharm Bull 29: 560-564, 2006.

  9. Funahashi T, Tanaka Y, Yamaori S, Kimura T, Matsunaga T, Ohmori S, Kageyama T, Yamamoto I, Watanabe K: Stimulatory effects of testosterone and progesterone on the NADH- and NADPH-dependent oxidation of 7beta-hydroxy-delta8- tetrahydrocannabinol to 7-oxo-delta8-tetrahydrocannabinol in monkey liver microsomes. Drug Metab Pharmacokinet 20: 358-367, 2005.

  10. Matsunaga T, Miyazato K, Cui L, Imamura T, Johkura K, Sasaki K, Ohmori S: Expressions of cytochrome P450 in differentiating mouse embryonic stem cells. Drug Metab Rev 37: 200, 2005.