Education

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

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

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

Professional Experience

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.

Research Area

Protein post-translational modifications such as ubiquitination and ubiquitin-like modification are key regulatory mechanisms that control various biological processes. Dysregulation of protein modification results in development of many human diseases like neurodegenerative disease and cancer. Our research interest has been focused on mechanism studies of ubiquitination and ubiquitin-like modification in regulation of cell proliferation, cell death, autophagy, and tumorigenesis. We are also working on identifying small-molecule modulators of E3 ubiquitin ligases that are critical for cancer development, which is emerging as a promising drug discovery strategy.

Selected publications (* indicates corresponding author,^#indicates co-first author)

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.