研究领域

蛋白翻译后修饰与肿瘤发生发展：蛋白质的泛素化和类泛素化修饰对于调节各种细胞和机体生物学活性都起着十分重要的作用，其调控的紊乱会导致包括神经退行性疾病和癌症在内的多种重大疾病的发生。我们致力于研究蛋白质泛素化和类泛素化修饰在调控细胞生长、死亡、自噬以及肿瘤发生发展中的作用和分子机理。同时，在分子机理研究的基础上，以在肿瘤发生发展中起重要作用的泛素连接酶为靶点，进行抗肿瘤新型靶向药物的研发，以期获得癌症治疗的新的先导化合物。

学习经历

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

工作经历

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，我校985平台特聘教授。

代表性成果

1. Zhang X#, Zhan Y#, Lin W, Zhao F, Guo C, Chen Y, Du M, Li D, Zhang L, An W*,Wang HR*, Xie P*. Smurf1 aggravates non-alcoholic fatty liver disease by stabilizing SREBP-1c in an E3 activity-independent manner.FASEB J, 2020, 34(6):7631-7643.
2. Wu Q#, Li G#, Wen C#, Zeng T#, Fan Y, Liu C, Fu GF, Xie C, Lin Q, Xie L, Huang L, Pu P, Ouyang Z, Chan HL, Zhao TJ, Chen XL*, Fu G*,Wang HR*.Mono-ubiquitination of p120-catenin is essential for TGFb-induced epithelial- mesenchymal transition and tumor metastasis.Science Advances, 2020, 6(4):eaay9819.
3. Tian M#, Zeng T#, Han S, Lin H, Lin Q, Li L, Jiang T, Li G, Zhang T, Kang Q, Deng X*,Wang HR*. A cell-based high-throughput screening method based on a ubiquitin-reference technique for identifying modulators of E3 ligases.J Biol Chem,2019, 294(8): 2880–2891.
4. Wang J#, Hao JW#, Wang X#, Guo H#, Sun HH, Lai XY, Liu LY, Zhu M, Wang HY, Li YF, Yu LY, Xie C,Wang HR, Mo W, Zhou HM, Chen S, Liang G, Zhao TJ*. DHHC4 and DHHC5 Facilitate Fatty Acid Uptake by Palmitoylating and Targeting CD36 to the Plasma Membrane.Cell Reports, 2019, 26(1):209-221.
5. Liu M#, Zeng T#, Zhang X#, Liu C, Wu Z, Yao L, Xie C, Xia H, Lin Q, Xie L, Zhou D, Deng X, Chan HL, Zhao TJ*,Wang HR*. ATR/Chk1 signaling induces autophagy through sumoylated RhoB-mediated lysosomal translocation of TSC2 after DNA damage.Nat Commun, 2018, 9:4139.
6. Jiang J#, Gui F#, He Z#, Li L, Li Y, Li S, Wu X, Deng Z, Sun X, Huang X, Huang W, Han S, Zhang T, Wang Z, Jiao B, Song S,Wang H, Chen L, Zhou D, Liu Q, Ren R*, Zhang J*, Deng X*. Targeting BRK-Positive Breast Cancers with Small-Molecule Kinase Inhibitors.Cancer Res. 2017, 77(1):175-186.
7. Wang X#, Zhao X#, Feng C, Weinstein A, Xia R, Wen W, Lv Q, Zuo S, Tang P, Yang X, Chen X,Wang H, Zang S, Stollings L, Denning TL, Jiang J, Fan J, Zhang G, Zhang X, Zhu Y, Storkus W, Lu B*. IL-36γ Transforms the Tumor Microenvironment and Promotes Type 1 Lymphocyte- Mediated Antitumor Immune Responses.Cancer Cell, 2015, 28(3):296-306
8. Wu H#, Wei L#, Fan F#, Ji S#, Zhang S, Geng J, Hong L, Fan X, Chen Q, Tian J, Jiang M, Sun X, Jin C, Yin ZY, Liu Q, Zhang J, Qin F, Lin KH, Yu JS, Deng X,Wang HR, Zhao B, Johnson RL, Chen L*, Zhou D*. Integration of Hippo signalling and the unfolded protein response to restrain liver overgrowth and tumorigenesis.Nat Commun, 2015, 6:6239.
9. Geng J#, Sun X#, Wang P, Zhang S, Wang X, Wu H, Hong L, Xie C, Li X, Zhao H, Liu Q, Jiang M, Chen Q, Zhang J, Li Y, Song S,Wang HR, Zhou R, Johnson RL, Chien KY, Lin SC, Han J, Avruch J, Chen L*, Zhou D*. Kinases Mst1 and Mst2 positively regulate phagocytic induction of reactive oxygen species and bactericidal activity.Nat Immunol,2015,16(11):1142-1152.
10. 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, 5:4901.
11. 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, 5:3733.
12. 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 Reports, 2014, 7(3): 871-882.
13. 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, 33(13): 1629-1639.
14. Ding F,Yin Z,Wang HR*. Ubiquitination in Rho signaling.CurrTop Med Chem, 2011, 11(23): 2879-87.
15. 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.
16. 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): 651-62.
17. 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.
18. 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.
19. Zhang Y,Wang HR, Wrana JL*. Smurf1: a link between cell polarity and ubiquitination.Cell Cycle, 2004, 3(4):391-2.
20.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.
21. 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.