More 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
Email Dr. Chen
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:
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.
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:
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:
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:
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.