Hangzhi CHEN, Ph.D.
1999-2003, B.Sc., School of Life Sciences, Xiamen University;
2003-2009, Ph.D., School of Life Sciences, Xiamen University;
2005 -2005, Visiting Students, Department of Biological Sciences, National University of Singapore.
2009-2012, Assistant professor, School of Life Sciences, Xiamen University;
2012-present, Associate professor, School of Life Sciences, Xiamen University.
We mainly focus on the biological functions of nuclear receptor, especially orphan nuclear receptor TR3 (also known as Nur77 or NGFI-B). TR3 plays an important roles in the processes of cell proliferation, differentiation and apoptosis. Since the specific ligand for TR3 has not been identified till now, the post-translational modifications of TR3 and its binding partners were considered as the main regulatory manner for TR3. We found that TR3 can inhibit growth of colorectal cancer via negatively regulating Wnt singaling activity. In colorectal cancer tissues, highly activated GSK3β induces hyper-phosphorylation of TR3, thereby disrupting the inhibitory effect of TR3 on Wnt signaling and stimulating the tumorigenesis of colorectal cancer. Moreover, Akt, ERK and Pin1 mediated post-translational modifications also influence the regulatory functions of TR3 on cell proliferation and cell death.
We will go on studying the functions of TR3 on digestive system cancer and metabolic syndrome through the regulation on cell metabolism, autophagy and apoptosis, and screening TR3 targeting compounds to interfere the development of this disease.
1. Chen HZ*, Wen Q, Wang WJ, He JP, Wu Q. The orphan nuclear receptor TR3/Nur77 regulates ER stress and induces apoptosis via interaction with TRAPγ. The International Journal of Biochemistry & Cell Biology, 2013, 45:1600–1609
2. Zhan YY, Chen Y, Zhang Q, Zhuang JJ, Tian M, Chen HZ, Zhang LR, Zhang HK, He JP, Wang WJ, Wu R, Wang Y, Shi CF, Yang K, Li AZ, Xin YZ, Li YT, Yang JY, Zheng ZH, Yu CD, Lin SC, Chang C, Huang PQ, Lin TW*, Wu Q*. The orphan nuclear receptor nur77 regulates LKB1 localization and activates AMPK. Nature Chemical Biology,2012, 8:897-904.
3. Chen HZ, Li L, Wang WJ, Du XD, Wen Q, He JP, Zhao BX, Li GD, Zhou W, Xia Y, Yang QY, Hew C-L, Liou Y-C*, Wu Q*. Prolyl isomerase Pin1 stabilizes and activates orphan nuclear receptor TR3 to promote mitogenesis. Oncogene, 2012, 31：2876-2887
4. Chen HZ, Liu QF, Li L, Wang WJ, Yao LM, Yang M, Liu B, Chen Wei, Zhan YY, Zhang MQ, Cai JC, Zheng ZH, Lin SC, Li BA*, Wu Q*. The orphan receptor TR3 suppresses intestinal tumorigenesis in mice by downregulating Wnt signaling. Gut, 2012, 61：714-724
5. Zhao BX, Chen HZ (co-first author), Du XD, Luo J, He JP, Wang RH, Wang Y, Wu R, Hou RR, Hong M, Wu Q* Orphan Receptor TR3 Enhances p53 Transactivation and Represses DNA Double-Strand Break Repair in Hepatoma Cells under Ionizing Radiation. Molecular Endocrinology, 2011, 25: 1337–1350
6. Lei NZ, Zhang XY, Chen HZ, Wang Yuan, Zhan YY, Zheng ZH, Shen YM, Wu Q*. A feed-back regulatory loop between methyltransferase PRMT1 and orphan receptor TR3. Nucleic Acids Res, 2009; 37, 832-848.
7. Chen HZ, Zhao BX, Zhao WX, Li L, Zhang B, Wu Q*. Akt phosphorylates the TR3 orphan receptor and blocks its targeting to the mitochondria. Carcinogenesis, 2008; 29, 2078-2088.
8. Zhan YY, Du XP, Chen HZ, Liu JJ, Zhao BX, Huang DH, Li GD, Xu QY, Zhang MQ, Bart C Weimer, Chen D, Cheng Z, Zhang LR, Li QX, Li SW, Zheng ZH, Song SY, Hang YJ, Ye ZY, Su WJ, Lin SC*, Shen YM*, Wu Q*. Cytosporone B is an agonist for nuclear orphan receptor Nur77. Nature Chemical Biology, 2008; 4, 548-556.
9. Chen HZ, Wu Q*. A novel function of p53 in TR3-MDM2 cross-talk. Cell Res, 2007; 17(4): 293-4.
10. Zhao BX, Chen HZ, Lei NZ, Li GD, Zhao WX, Zhan YY, Liu B, Lin SC, Wu Q*. p53 mediates the negative regulation of MDM2 by orphan receptor TR3. EMBO J, 2006; 25(24): 5703-15.