Sen Chen, PhD

About Sen Chen, PhD

SenDuring the MS period, Dr. Chen majored in Pharmaceutics in Dr. Zheng’s lab, where she had been focusing on biomaterials and drug delivery system. She worked at a pharmaceutical company for about 2 years after graduation, further strengthening her knowledge on biochemistry and drug development. Encouraged by the striking progress of bioengineering and its promising impact on drug development, she went to Japan and pursued her PhD degree in Dr. Kadomatsu’s lab on molecular biology. She focused on two projects. One was on Basigin/CD147 knock out mice. She clearly elucidated the effect of flanking genes and genetic background on the phenotype, and provided a useful means of investigating the biological function of Basigin. The other study was on Midkine (MK, a heparin binding growth factor) mediated signal transduction and its impact on cancer treatment. She continued this study in Dr. Kadomatsu’s lab as research fellow for another 2 years after graduation. Using a small Trapping Peptide (MK binding domain in its receptor), she successfully demonstrated the crucial role of MK-LRP1 signaling in anchorage-independent cell growth. She also worked on several MK projects including its biosynthesis, its roles in angiogenesis, cardiac ischemia as well as in childhood leukemia.

After that, Dr. Chen joined Dr. Steven P. Balk’s lab in BIDMC and continued her research on cancer biology. She has been focusing on the signal pathway and molecular mechanism involved in prostate cancer. She undertook the study on mechanisms that contribute to PI3 kinase activation in PTEN deficient prostate cancer cells. She found that the p110beta isoform of PI3 kinase was mediating basal activity independent of RTK, while the p110alpha mediated GF stimulated activation. She has also been studying the function of a non-receptor kinase termed Bmx, which is activated downstream of PI3 kinase and contributes to prostate cancer development. Using a positional scanning peptide library screen, she has identified that Bmx has a marked preference for substrates with a priming phosphotyrosine at -1 position, and further validated that Bmx phosphorylates multiple tyrosine kinases on their kinase domain and regulates their activity, which will have great implications for many cancers as well as metabolic diseases such as type 2 diabetes. She has also successfully developed a mouse prostate cancer model with inducible ERG expression in prostate. Given that TMPRSS2-ERG rearrangement occurs almost in half of the prostate cancer patients, this model will definitely be useful for elucidating the function mechanism of ERG on prostate cancer and contributing to the prostate cancer treatment. Meanwhile, she collaborates with other colleagues and contributes to understanding the molecular mechanism on castration resistance prostate cancer (CRPC), including intratumoral de novo androgen synthesis, AR-mediated gene expression, sox9 gene mediation in TMPRSS2:ERG positive prostate cancer, AR mediated p27 degradation as well as AR targeting drug development.

Email Dr. Chen

Positions

Research Fellow, Beth Israel Deaconess Medical Center / Harvard Medical School, Boston, MA: 2008-present

Global COE Research Fellowship, Nagoya University, Japan: 2005-2008

Global COE Research Assistantship, Nagoya University, Japan: 2003-2005

Education

Postdoctoral Training: Cancer Biology, Beth Israel Deaconess Medical Center, US: 2008-present

Postdoctoral Training: Medical Science, Nagoya University, Japan: 2005-2008

PhD: Medical Science, Nagoya University, Japan: 2001-2005

MS: Pharmaceutics, Shenyang Pharmaceutical University, China: 1994-1997

BS: Pharmaceutics, Shenyang Pharmaceutical University, China: 1990-1994

Grants and Awards

JSPS Young Researcher Scholarship, Nagoya University, Japan: 2001-2002

LiaoNing Province Education Committee Scientific Technology Promotion Award for Junior Researcher: 1998

Publications 

  1. F. Ma, H. Ye, H. H. He, S. J. Gerrin, S. Chen, B. Tanenbaum, C. Cai, A. G. Sowalsky, L. He, H. Wang, S. P. Balk, and X. Yuan. SOX9 drives WNT pathway activation in prostate cancer . J Clin Invest. 2016;126(5):1745-1758. doi:10.1172/JCI78815. Epub 2016 Apr 4.

  2. Gao S, Ye H, Gerrin S, Wang H, Sharma A, Chen S, Patnaik A, Sowalsky AG, Voznesensky O, Han W, Yu Z, Mostaghel EA, Nelson PS, Taplin ME, Balk SP, Cai C. ErbB2 Signaling Increases Androgen Receptor Expression in Abiraterone-Resistant Prostate Cancer. Clin Cancer Res. 2016 Mar 2. [Epub ahead of print]PMID: 26936914

  3. Chen S , Cai C, Simon NI, Yuan X, Gray NS, Balk SP. (2014) Bmx mediates CRPC growth through regulating multiple RTK. (In Preparation)

  4. Yu Z, Chen S, Sowalsky AG, Voznesensky OS, Mostaghel EA, Nelson PS, Cai C, Balk SP. Rapid Induction of Androgen Receptor Splice Variants by Androgen Deprivation in Prostate Cancer (2014). Clin Cancer Res. 20(6):1590-1600.

  5. Liu F, Zhang X, Weisberg E, Chen S, Hur W, Wu H, Zhao Z, Wang W, Mao M, Cai C, Simon NI, Sanda T, Wang J, Look AT, Griffin JD, Balk SP*, Liu Q*, and Gray NS*. (2013) Discovery of a Selective Irreversible BMX Inhibitor for Prostate Cancer. ACS Chemical Biology . 8(7):1423-1428.

  6. 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.

  7. S. Chen , X. Jiang, C. A. Gewinner, J. M. Asara, N. I. Simon, C. Cai, L. C. Cantley, S. P. Balk, Tyrosine Kinase BMX Phosphorylates Phosphotyrosine-Primed Motif Mediating the Activation of Multiple Receptor Tyrosine Kinases. Sci. Signal. 6, ra40 (2013).

  8. Cai C, Wang H, He HH, Chen S, He L, Ma F, Mucci L, Wang Q, Fiore C, Sowalsky AG, Loda M, Liu XS, Brown M, Balk SP & Yuan X. (2013) ERG Induces Androgen Receptor-mediated Regulation of SOX9 in Prostate Cancer. ( Journal of Clinical Investigation) 1;123(3): 1109-22

  9. Shen H, Shanmugasundaram K, Simon NI, Cai C, Wang H, Chen S, Balk SP & Rigby AC. (2012) In Silico Discovery of Androgen Receptor Antagonists with Activity in Castration Resistant Prostate Cancer. ( Molecular Endocrinology). 26(11):1836-46

  10. Wang H, Xu Y, Fang Z, Chen S, Balk SP and Yuan X. (2012) Doxycycline Regulated Induction of AKT in Murine Prostate Drives Proliferation Independently of p27 Cyclin Dependent Kinase Inhibitor Downregulation. ( PLOS One). 7(7): e41330

  11. Fang Z, Zhang T, Dizeyi N, Chen S, Wang H, Swanson KD, Cai C, Balk SP and Yuan X. (2012) Androgen Receptor Enhances p27 Degradation in Prostate Cancer Cells Through Rapid and Selective TORC2 Activation. The Journal of Biological Chemistry. 13;287(3):2090-8.

  12. Cai C, He HH, Chen S, Coleman I, Wang H, Fang Z, Chen S, Nelson PS, Liu XS, Brown M, and Balk SP. (2011) Androgen receptor gene expression in prostate cancer is directly suppressed by the androgen receptor through recruitment of lysine specific demethylase 1. Cancer Cell. 20(4):457-71.

  13. Cai C, Chen S, Ng P, Mostaghel EA, Marck B, Matsumoto AM, Simon, NI, Wang H, Chen S, and Balk SP. (2011) Intratumoral de novo steroid synthesis activates androgen receptor in castration resistant prostate cancer and is upregulated by treatment with CYP17A1 inhibitors. Cancer Research. 71(20):6503-13.

  14. Sakamoto K, Bu GJ, Chen S, Takei Y, Hibi K, Kodera Y, McCormick LM, Nakao A, Noda M, Muramatsu T, and Kadomatsu K. (2011) Premature Ligand-Receptor Interaction during Biosynthesis Limits the Product in of Growth Factor Midkine and Its Receptor LDL Receptor-related Protein 1. The Journal of Biological Chemistry. 286(10): 8405-8413.

  15. Jiang XN, Chen S, Asara JM, and Balk SP. (2010) Phosphoinositide 3-Kinase Pathway Activation in Phosphate and Tensin Homolog (PTEN)-deficient Prostate Cancer Cells Is Independent of Receptor Tyrosine Kinases and Mediated by the p110 beta and p110 delta Catalytic Subunits. The Journal of Biological Chemistry. 285(20):14980-14989.

  16. Narita H, Chen S, Komori K, and Kadomatsu K. (2008) Midkine is expressed by infiltrating macrophages in in-stent restenosis in hypercholesterolemic rabbits. Journal of Vascular Surgery. 47(6): 1322-1329.

  17. Chen S , Bu G, Takei Y, Sakamoto K, Ikematsu S, Muramatsu T, and Kadomatsu K. (2007) Journal of Cell Science. 120(Pt 22): 4009-4015.

  18. Hidaka H, Yagasaki H, Takahashi Y, Hama A, Nishio N, Tanaka M, Yoshida N, Villalobos IB, Wang Y, Xu Y, Horibe K, Chen S, Kadomatsu K, and Kojima S. (2007) Increased midkine gene expression in childhood B-precursor acute lymphoblastic leukemia. Leukemia Research. Aug 31(8):1053-1059.

  19. Horiba M, Kadomatsu K, Yasui K, Lee JK, Takenaka H, Sumida A, Kamiya K, Chen S, Sakuma S, Muramatsu T, and Kodama I. (2006) Midkine plays a protective role against cardiac ischemia/reperfusion injury through a reduction of apoptotic reaction. Circulation . 114(16):1713-1720.

  20. Chen S , Kadomatsu K, Kondo M, Toyama Y, Toshimori K, Ueno S, Miyake Y, Muramatsu T. (2004) Effects of flanking genes on the phenotypes of mice deficient in basigin/CD147. Biochemical and Biophysical research communications. 324(1):147-153.

  21. Chen S , and Zheng J. (2000) The observation on in vitro permeation and Irritation of Nimodipine Paches. Journal of Shenyang Pharmaceutical University. 17(2):84-87.

  22. Chen S , Zheng J, Hao J, and Wu H. (1999) Effect of Penetration Enhancers and Iontophoresis on Nimodipine in Vitro Permeation. Journal of Shenyang Pharmaceutical University. 16(2):95-98.

Chapters Edition

  1. Pharmaceutical Coating Technology (Chinese Version Translation) (2001) (Original Author: Graham Cole, John Hogan, Michael Auton). China Medical Technology Press. ISBN: 7506723654
  2. Dermal and Transdermal delivery system (1997 original version; 2006 modified new version) People’s Health Press. ISBN: 7-117-08178-3.