Assistant Adjunct Professor of Pharmacology
Ph.D., Huazhong University of Science and Technology
My research interest is to elucidate the molecular and cellular mechanisms involved in the regulation of the xenobiotic metabolizing enzymes, particularly the Phase II UDP-glucuronosyltransferases (UGTs) by utilizing the genetically modified mouse models. We recently created humanized UGT1 mice, in which humoral and developmental regulation of the human UGT1 genes and the onset of neonatal hyperbilirubinemia have been investigated. We discovered the repressive actions of the nuclear receptor PXR on neonatal UGT1A1 gene expression. We are exploring the interplay between PXR and its co-repressors NCoR and SMRT in chromatin remodeling for the de-repression of the UGT1A1 gene by ChIP-sequencing. With the recent development of floxed Ugt1 mice, we are defining the importance of tissue-specific glucuronidation in preventing druginduced toxicities, and we have illustrated the contributory mechanism for intestinal damage caused by the chemotherapeutic drug CPT-11. Our experimental findings may have an impact on developing more eff ective chemotherapy with the use of CPT-11.
Chen S, Nguyen N, Tamura K, Karin M and Tukey RH. The role of the Ah-receptor and p38 in Benzo(a)pyrene-7,8-dihydrodiol and Benzo(a) pyrene-7,8-dihydrodiol- 9,10-epoxide induced apoptosis. (JBC, 278: 19526-19533, 2003)
Chen S, Operana T, Bonzo J, Nguyen N, Tukey RH. Erk kinase inhibition stabilizes the Ah receptor. Implications for transcriptional activation and protein degradation. (JBC, 280: 4350-4359, 2005)
Chen S, Beaton D, Nguyen N, Senekeo-Eff enberger K, Brace-Sinnokrak E, Ritter JK and Tukey RH. Tissue specific, inducible, and hormonal control of the human UDP-Glucuronosyltransferase-1 (UGT1) locus. (JBC, 280: 37547-37557, 2005)
Chen S, Yueh MF, Evans RM, Tukey RH. Pregnane-x-receptor controls hepatic glucuronidation during pregnancy and neonatal development in humanized UGT1 mice. (Hepatology, 56:658-67, 2012)
Chen S, Yueh MF, Bigo C, Barbier O, Wang K, Karin M, Nguyen, N, and Tukey RH, Intestinal glucuronidation protects against chemotherapy induced toxicity by irinotecan (CPT-11), PNAS, 2013. Revised.