Sen Chen, PhD
About Sen Chen, PhD
During 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.
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
-
Chen S , Cai C, Simon NI, Yuan X, Gray NS, Balk SP. (2014) Bmx mediates CRPC growth through regulating multiple RTK. (In Preparation)
-
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.
-
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.
-
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.
-
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.
-
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.
-
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.
-
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.
-
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.
-
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
-
Pharmaceutical Coating Technology (Chinese Version Translation) (2001) (Original Author: Graham Cole, John Hogan, Michael Auton). China Medical Technology Press. ISBN: 7506723654
-
Dermal and Transdermal delivery system (1997 original version; 2006 modified new version) People’s Health Press. ISBN: 7-117-08178-3.