shao-yongMore than 10 years ago before Dr. Chen came to USA, he studied biosynthesis of steroids by fungi in China. His scientific journey on the molecular basis of prostate cancer (PCa) development and androgen receptor (AR) regulation was started since he worked as a Ph.D. student in USA. His Ph.D. dissertation work was mainly focused on several co-factors of AR-mediated transcription and AR-dependent transcriptome. His research at BIDMC (Harvard Medical School) was initiated with the unexpected finding that the peptidyl-prolyl isomerase Pin1 has opposite effects on the AR and Wnt pathways. This work led to the realization the importance of studying AR phosphorylation. For the past few years, he has investigated the mechanisms and significance of AR phosphorylation and dephosphorylation at the molecular and cellular levels. His future direction is to continue the study of AR regulation and to identify updated strategies to overcome advanced PCa diseases. His research contains basic and translational components and should have both biological and clinical impacts on prostate cancer research.

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1: Yuan X, Cai C, Chen S, Chen S, Yu Z, Balk SP. Androgen receptor functions in castration-resistant prostate cancer and mechanisms of resistance to new agents targeting the androgen axis (2013). Oncogene. Jun 10. doi: 10.1038/onc.2013.235.

2: Jin D, Li R, Mao D, Luo N, Wang Y, Chen S, Zhang S. Mitochondria-localized glutamic acid-rich protein (MGARP) gene transcription is regulated by Sp1. PLoS One. 2012;7(11):e50053. doi: 10.1371/journal.pone.0050053. PMID: 23209644; PMCID: PMC3507827.

3: Ding X, Jiang QB, Li R, Chen S, Zhang S. NOK/STYK1 has a strong tendency towards forming aggregates and colocalises with epidermal growth factor receptor in endosomes. Biochem Biophys Res Commun. 2012;421(3):468-73. PMID: 22516751.

4: Chen S, Gulla S, Cai C, Balk SP. Androgen receptor serine 81 phosphorylation mediates chromatin binding and transcriptional activation. J Biol Chem. 2012;287(11):8571-83. PMID: 22275373.

5: Sun T, Yang M, Chen S, Balk S, Pomerantz M, Hsieh CL, Brown M, Lee GS, Kantoff PW. The altered expression of MiR-221/-222 and MiR-23b/-27b is associated with the development of human castration resistant prostate cancer. Prostate. 2011. doi: 10.1002/pros.22456. PMID: 22127852.

6: Cai C, He HH, Chen S, Coleman I, Wang HY, Fang Z, Chen SY, Nelson PS, Liu XS, Brown M, Balk SP. Androgen Receptor Gene Expression in Prostate Cancer is Directly Suppressed by the Androgen Receptor through Recruitment of Lysine Specific Demethylase 1. Cancer Cell, 2011;20(4):457-71. PMID: 22014572; PMCID: PMC3225024.

7: Cai C, Chen S, Ng P, Bubley GJ, Nelson PS, Mostaghel EA, Marck B, Matsumoto AM, Simon N, Wang H, Chen S, Balk SP. Intratumoral De Novo Steroid Synthesis Activates Androgen Receptor in Castration Resistant Prostate Cancer and is Upregulated by Treatment with CYP17A1 Inhibitors. Cancer Res. 2011;71(20):6503-13. PMID: 21868758; PMCID: PMC3209585.

8: Chen SY, Kesler CT, Paschal BM, Balk SP. Androgen receptor phosphorylation and activity are regulated by an association with protein phosphatase 1. J Biol Chem. 2009, 284(38):25576-84. PMID: 19622840; PMCID: PMC2757959.

9: Cai C, Wang H, Xu Y, Chen S, Balk SP. Reactivation of androgen receptor-regulated TMPRSS2:ERG gene expression in castration-resistant prostate cancer. Cancer Res. 2009, 69(15):6027-32. PMID:19584279; PMCID: PMC2859723.

10: Cai C, Portnoy DC, Wang H, Jiang X, Chen S, Balk SP. Androgen receptor expression in prostate cancer cells is suppressed by activation of epidermal growth factor receptor and ErbB2. Cancer Res. 2009, 69(12):5202-9. doi: 10.1158/0008-5472.CAN-09-0026. PMID: 19491261.

11: Bhatt RS, Landis DM, Zimmer M, Torregrossa J, Chen S, Sukhatme VP, Iliopoulos O, Balk S, Bubley GJ. Hypoxia-inducible factor-2alpha: effect on radiation sensitivity and differential regulation by an mTOR inhibitor. BJU Int. 2008;102(3):358-63. doi: 10.1111/j.1464-410X.2008.07558.x. PMID: 18394010.

12: Hsieh CL, Cai C, Giwa A, Bivins A, Chen SY, Sabry D, Govardhan K, Shemshedini L. Expression of a hyperactive androgen receptor leads to androgen-independent growth of prostate cancer cells. J Mol Endocrinol. 2008, 41(1):13-23. PMID: 18469090.

13: Cai C, Hsieh CL, Omwancha J, Zheng Z, Chen SY, Baert JL, Shemshedini L. ETV1 is a novel androgen receptor-regulated gene that mediates prostate cancer cell invasion. Mol Endocrinol. 2007; 21(8):1835-46. PMID: 17505060.

14: Cai C, Chen SY, Zheng Z, Omwancha J, Lin MF, Balk SP, Shemshedini L. Androgen regulation of soluble guanylyl cyclasealpha1 mediates prostate cancer cell proliferation. Oncogene. 2007, 26(11): 1606-15. PMID: 16964290.

15: Chen SY, Xu Y, Yuan X, Bubley GJ, Balk SP. Androgen receptor phosphorylation and stabilization in prostate cancer by cyclin-dependent kinase 1. Proc Natl Acad Sci U S A. 2006; 103(43):15969-74. PMID: 17043241; PMCID: PMC1635111.

16: Chen SY, Cai C, Fisher CJ, Zheng Z, Omwancha J, Hsieh CL, Shemshedini L. c-Jun enhancement of androgen receptor transactivation is associated with prostate cancer cell proliferation. Oncogene. 2006; 25(54):7212-23. (Co-first author). PMID: 16732317.

17: Chen SY, Wulf G, Zhou XZ, Rubin MA, Lu KP, Balk SP. Activation of beta-catenin signaling in prostate cancer by peptidyl-prolyl isomerase Pin1-mediated abrogation of the androgen receptor-beta-catenin interaction. Mol Cell Biol. 2006; 26(3):929-39. PMCID: PMC1347015.

18: Xu Y, Chen SY, Ross KN, Balk SP. Androgens induce prostate cancer cell proliferation through mammalian target of rapamycin activation and post-transcriptional increases in cyclin D proteins. Cancer Res. 2006; 66(15):7783-92. PMID: 16885382.

19: Omwancha J, Zhou XF, Chen SY, Baslan T, Fisher CJ, Zheng Z, Cai C, Shemshedini L. Makorin RING finger protein 1 (MKRN1) has negative and positive effects on RNA polymerase II-dependent transcription. Endocrine. 2006; 29(2):363-73. PMID: 16785614.

20: Zheng Z, Cai C, Omwancha J, Chen SY, Baslan T, Shemshedini L. SUMO-3 enhances androgen receptor transcriptional activity through a sumoylation-independent mechanism in prostate cancer cells. J Biol Chem. 2006; 281(7):4002-12. PMID: 16361251.

21: Masiello D, Chen SY, Xu Y, Verhoeven MC, Choi E, Hollenberg AN, Balk SP. Recruitment of beta-catenin by wild-type or mutant androgen receptors correlates with ligand-stimulated growth of prostate cancer cells. Mol Endocrinol. 2004; 18(10):2388-401. PMID: 15256534.

22: Salas TR, Kim J, Vakar-Lopez F, Sabichi AL, Troncoso P, Jenster G, Kikuchi A, Chen SY, Shemshedini L, Suraokar M, Logothetis CJ, DiGiovanni J, Lippman SM, Menter DG. Glycogen synthase kinase-3 beta is involved in the phosphorylation and suppression of androgen receptor activity. J Biol Chem. 2004; 279(18):19191-200. PMID: 14985354.

23: Bubulya A, Chen SY, Fisher CJ, Zheng Z, Shen XQ, Shemshedini L. c-Jun potentiates the functional interaction between the amino and carboxyl termini of the androgen receptor. J Biol Chem. 2001, 276(48):44704-11. (Co-first author). PMID: 11577103.

24: Shenk JL, Fisher CJ, Chen SY, Zhou XF, Tillman K, Shemshedini L. p53 represses androgen-induced transactivation of prostate-specific antigen by disrupting hAR amino- to carboxyl-terminal interaction. J Biol Chem. 2001; 276(42):38472-9. PMID: 11504717.