Wenyi . Wei, Ph.D.
Dept. of Pathology
Director, Biochemistry Program
Cancer Research Institute, BIDMC Cancer Center
Beth Israel Deaconess Medical Center
Harvard Medical School
330 Brookline Avenue, E/CLS-637
Boston, MA 02215
Office Phone: 617-735-2495
Office Fax: 617-735-2480
Dr. Wenyi Wei received his B.A. degree from Shandong University in 1993 and then obtained his M.S. training in Chinese Academy of Science from 1993 to 1996. Afterwards, Dr. Wei received his Ph.D. training in the MCB department at Brown University and his postdoctoral training in the laboratory of Dr. William Kaelin, Jr. at DFCI, Harvard Medical School. Dr. Wei became independent from October 2006 in Department Pathology at Beth Israel Deaconess Medical Center, Harvard Medical School. The major focus of the WEI laboratory is aimed at understanding how APC and SCF activities contribute to cell cycle regulation and subsequent tumor formation. To achieve these goals, the lab will use multidisciplinary approaches including biochemical and genetic analysis. In the long term, we hope that a better understanding of the multilayer regulation of the delicate proteolysis pathways will lead us to the design of more efficient intervention strategies to combat cancer, cardiovascular disorders and other human diseases.
Basic Research - Aberrant cell cycle regulation leads to various human disease including cancer and cardiovascular disorders. Proper cell cycle transitions are driven by waves of ubiquitin-dependent degradation of key cell cycle regulators by APC or SCF, the two major E3 ligase complexes. My previous research demonstrated that APC/Cdh1 complex ubiquitinates and thus targets Skp2 for degradation in early G1 phase. This finding provides important insights into why SCF and APC activity is mutually exclusive and how the orchestration of SCF and APC activity affects cell cycle progression. More importantly, it also impinges on the function of Cdh1 as a tumor suppressor. I am also interested in understanding how SCF complexes regulate the G1-S transition by degradation of their specific substrates.
The major focus of research in my laboratory is aimed at understanding how APC and SCF activities contribute towards cell cycle regulation and subsequent tumor formation. More specifically, I am interested in elucidating the underlying mechanisms that define the oscillation of APC and SCF activity in different cell cycle phases. Currently I am pursuing the underlying mechanisms that timely regulate APC/Cdh1 activity in different cell cycle phases. Additionally, I am also interested in understanding whether other layers of crosstalk between the APC and SCF complex exist. Furthermore, I would like to identify novel downstream targets for both APC and SCF complexes, which will help pinpoint their functions in both cell cycle control and tumor formation. To this end, I have developed biochemical purification approaches that would allow me to identify novel downstream targets for APC/Cdh1 and SCF/Fbw7 complexes. In addition, I am also interested in defining the tumor suppressor function of Cdh1 utilizing conditional Cdh1 knockout mice. To achieve these goals, my lab will use multidisciplinary approaches including biochemical and genetic analysis. In the long term, I hope that a better understanding of the multilayer regulation of the delicate proteolysis pathways will lead us to the design of more efficient intervention strategies to combat cancer, cardiovascular disorders and other human diseases.
New and Noteworthy Publications:
Guo, J., Chakraborty, A. K., Liu, P., Gan, W., Zheng, X., Inuzuka, H., Wang, B., Zhang, J., Zhang, L., Novak, J., Yuan, M., Cheng, J. Q., Toker, A., Signroretti, S., Zhang, Q., Asara, J. M., Kaelin, Jr., W. G., and Wei, W. . (2016) pVHL suppresses kinase activity of Akt in a proline-hydroxylation dependent manner. Science 353(6302):929-32..
Zhang, J. *, Xu, K. *, Liu, P., Geng, Y., Wang, B., Gan, W., Guo, J., Wu, F., Chin, Y. R., Berrios, C., Lien, E. C., Toker, A., DeCaprio, J. A., Sicinski, P. and Wei, W. . (2016) Inhibition of Rb phosphorylation leads to mTORC2-mediated activation of Akt. Molecular Cell 62(6):929-42..
Liu, P., Gan, W., Chin, Y. R., Ogura, K., Guo, J., Zhang, J., Wang, B., Blenis, J., Cantley, L.C., Toker, A., Su, B.# and Wei, W.# . (2015) PtdIns(3,4,5)P3-dependent activation of the mTORC2 Kinase Complex. Cancer Discovery 5(11):1194-209..
Gan, W.*, Dai, X.*, Lunardi, A.*, Li, Z.*, Inuzuka, H., Liu, P., Varmeh, S., Zhang, J., Cheng, L., Sun, Y., Asara, J. M., Beck, A. H., Huang, J., Pandolfi, P. P.# and Wei, W.# . (2015) SPOP promotes ubiquitination and degradation of the ERG oncoprotein to suppress prostate cancer progression. Molecular Cell 59(6):917-30..
Liu, P.*, Gan, W.*, Guo, C., Xie, A., Gao, D., Guo, J., Zhang, J., Willis, N., Su, A., Asara, J. M., Scully, R. and Wei, W. . (2015) Akt-mediated phosphorylation of XLF impairs non-homologous end joining DNA repair. Molecular Cell 57(4): 648-661..
Wan, L., Tan, M., Yang, J., Inuzuka, H., Dai, X., Wu, T., Liu, J., Shaik, S., Chen, G., Deng, J., Malumbres, M., Letai, A., Kirschner, M. W., Sun, Y. and Wei, W. . (2014) APCCdc20 suppresses apoptosis through targeting Bim for ubiquitination and destruction Developmental Cell 29(4):377-91.