王洪睿 WANG Hong-Rui, Ph.D.

教授，博士生导师

课题组组长

电  话：+86-592-2181167

E-mail：wanghr@xmu.edu.cn

1992年，清华大学获学士学位；

1994年，清华大学获硕士学位；

1996年，中国科学院生物物理研究所获博士学位；

1996-1999年，美国加州理工大学博士后；

1999-2002年，加拿大多伦多西乃山医院研究所博士后；

2002-2008年，加拿大多伦多西乃山医院研究所高级研究助理；

2008年至今，厦门大学985平台特聘教授。

1992, B.Sc., Biochemistry, Tsinghua University;

1994, M.Sc., Biochemistry, Tsinghua University;

1996, Ph.D., Molecular Biology, Institute of Biophysics, Chinese Academy of Science;

1996-1999, Postdoctoral Scholar, Division of Biology, California Institute of Technology, Pasadena, USA;

1999-2002, Postdoctoral Fellow, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada;

2002-2008, Senior Research Associate, Samuel Lunenfeld Research Institute, Mount Sinai, Hospital, Toronto, Canada;

2008-Present, Professor of School of Life Sciences, Xiamen University. 

研究领域（Research Area）

细胞极性的建立对于所有的真核细胞都有着极其重要的作用。由于其重要的生物学意义，从低等到高等生物中细胞极性的调节机制是非常保守的。我们的研究主要致力于TGFbeta途径及其泛素信号在细胞极性调节，特别是在癌症发生过程中细胞运动和上皮－间质细胞转化中的细胞极性调节中的作用。

我们同时开发出一个以细胞作为平台的高通量筛选系统，可以作为有效的手段来筛选一些在癌症或其它疾病中起重要作用的E3泛素连接酶的小分子抑制剂，从而作为新药开发的先导化合物。

Cell polarity is a fundamental property that controls a wide range of cell behavior in all eukaryotic cells. Recent studies have suggested that regulation of polarity in many biological processes is through a molecular mechanism that is conserved from worms to mammals. Our research interest has  signaling and ubiquitin-dependentbbeen focused on functional studies of TGF proteasome pathway in regulation of cell polarity during directed cell migration and epithelial-mesenchymal transition (EMT).

Accumulating evidence suggests that E3 ubiquitin ligases are involved in development of many human diseases. Search for small molecule modulators of these E3 ubiquitin ligases is emerging as a promising drug discovery strategy. We developed a novel cell-based high-throughput screening system to look for small molecule modulators of E3 ubiquitin ligases. We expect this system will provide us a powerful drug screening tool for therapeutics. 

代表性论文 (Selected Publications)    

1.     Wang M, Guo L, Wu Q, Zeng T, Lin Q, Qiao Y, Wang Q, Liu M, Zhang X, Ren L, Zhang S, Pei Y, Yin Z, Ding F, Wang HR*. ATR/Chk1/Smurf1 pathway determines cell fate after DNA damage by controlling RhoB abundance.Nat Commun. 2014 Sep 24;5:4901.

2.     Zeng T, Wang Q, Fu J, Lin Q, Bi J, Ding W, Qiao Y, Zhang S, Zhao W, Lin H, Wang M, Lu B, Deng X, Zhou D, Yin Z*, Wang HR*.Impeded Nedd4-1-Mediated Ras Degradation Underlies Ras-Driven Tumorigenesis Cell Rep. 2014 May 8;7(3):871-82. 

3.  Xie P, Zhang M, He S, Lu K, Chen Y, Xing G, Lu Y, Liu P, Li Y, Wang S, Chai N, Wu J, Deng H, Wang HR, Cao Y, Zhao F, Cui Y, Wang J, He F, Zhang L*. The covalent modifier Nedd8 is critical for the activation of Smurf1 ubiquitin ligase in tumorigenesis. Nat Commun. 2014 May 13;5:3733.

4.     Lin H, Lin Q, Liu M, Lin Y, Wang X, Chen H, Xia Z, Lu B, Ding F, Wu Q, Wang HR*. PKA/Smurf1 signaling-mediated stabilization of Nur77 is required for anticancer drug cisplatin-induced apoptosis. Oncogene. 2014 Mar 27;33(13): 1629-39.

5.   Ding F, Yin Z, Wang HR*. Ubiquitination in Rho signaling. Curr Top Med Chem, 2011, 11(23): 2879-87.

6.   Tian M, Bai C, Lin Q, Lin H, Liu M, Ding F, Wang HR*. Binding of RhoA by the C2 domain of E3 ligase Smurf1 is essential for Smurf1-regulated RhoA ubiquitination and cell protrusive activity. FEBS lett, 2011, 585(14): 2199-04.

7.   Wang L, Liu YT, Hao R, Chen L, Chang Z, Wang HR, Wang ZX, Wu JW. Molecular mechanism of the negative regulation of Smad1/5 by carboxyl terminus of Hsc70-interacting protein (CHIP). J Biol Chem, 2011, 286(18): 15883-94.

8.   Wiesner S, Ogunjim AA, Wang HR, Rotin D, Sicheri F, Wrana JL, Forman-Kay JD. Autoinhibition of the HECT-type ubiquitin ligase Smurf2 through its C2 domain. Cell, 2007, 130(4):651-662

9.   Wang HR, Ogunjimi AA, Zhang Y, Ozdamar B, Bose R, Wrana JL. Degradation of RhoA by Smurf1 ubiquitin ligase. Methods Enzymol, 2006, 406:437-47.

10.   Ozdamar B, Bose R, Barrios-Rodiles M, Wang HR, Zhang Y, Wrana JL. Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity. Science, 2005, 307(5715):1603-9.

11.Zhang Y, Wang HR, Wrana JL. Smurf1: a link between cell polarity and ubiquitination. Cell Cycle, 2004, 3(4):391-2.

12.Wang HR, Zhang Y, Ozdamar B, Ogunjimi AA, Alexandrova E, Thomsen GH, Wrana JL. Regulation of cell polarity and protrusion formation by targeting RhoA for degradation. Science, 2003, 302(5651):1775-9.

13.Bonni S, Wang HR, Causing CG, Kavsak P, Stroschein SL, Luo K, Wrana JL.TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation. Nat Cell Biol, 2001, 3(6):587-95.