Dr Liang Wu

Tel: (+44) (0)1904 32 8278
Email: liang.wu@york.ac.uk

Postdoctoral Research Associate

Research interests

I have been a PDRA in the group of Prof. Gideon Davies, FRS, FMedSci since 2013.  I am broadly interested in the characterization of human carbohydrate processing enzymes involved in 1) heparan sulfate metabolism and 2) lysosomal storage disorders.

My research led to the first crystal structures of human heparanase (Wu et al, Nat. Struct. Mol. Biol., 2015; Wu et al, Nat. Chem. Biol., 2017), the main enzyme responsibe for heparan sulfate breakdown and a major promoter of aggressive metastatic cancers.

In collaboration with Hermen Overkleeft (University of Leiden, Netherlands), I have been heavily involved in the development of activity-based probes to visualize glycoside hydrolases.  Such probes can be used to diagnose enzyme deficiencies in lysosomal storage disorders such as Pompe disease (Jiang et al, ACS Cent. Sci., 2016) and Fabry disease (Artola et al, Chem. Sci., 2019).   

Most recently I was awarded an EMBO short term fellowship to visit the laboratory of Prof. Israel Vlodavsky (Technion Institute, Israel). We are investigating the anti-cancer potential of novel heparanase inhibitors (also with Hermen Overkleeft), and the biological function of the relatively uncharacterized protein heparanase-2. 

Selected recent publications

  • α-D-Gal-cyclophellitol cyclosulfamidate is a Michaelis complex analog that stabilizes therapeutic lysosomal α-galactosidase A in Fabry disease
    Artola et al, Chemical Science, 2019, In press
  • An overview of activity-based probes for glycosidases
    Wu et al, Current Opinion in Chemical Biology, 2019, 53, 25-36
  • Dynamic and functional profiling of xylan-degrading enzymes in Aspergillus secretomes using activity based probes
    Schröder et al., ACS Central Science, 2019, 5, 1067-1078
  • An overview of the structure, mechanism and specificity of human heparanase
    Wu L. and Davies G. J., in Heparanase - From basic research to clinical applications, Vlodavsky I., Sanderson R. D. and Ilan, N. Ed., 2019, In press
  • Gluco-1H-imidazole; a new class of azole-type β-glucosidase inhibitor
    Schröder et al., J Am Chem Soc, 2018, 140, 5045-5048
  • Activity based probes for functional interrogation of retaining β-glucuronidases
    Wu et al., Nature Chemical Biology, 2017, 13, 867–873
  • A fluorescence polarization activity-based protein profiling assay in the discovery of potent, selective inhibitors for human non-lysosomal glucosylceramidase
    Lahav et al., J Am Chem Soc, 2017, 139, 14192-14197
  • 1,6-Cyclophellitol cyclosulfates: A new class of irreversible glycosidase inhibitor
    Artola et al., ACS Central Science, 2017, 3, 784-793
  • Detection of active mammalian GH31 α‑Glucosidases in health and disease using in-class, broad-spectrum activity-based probes
    Jiang et al., ACS Central Science, 2016, 2, 351-358
  • Structural characterization of human heparanase reveals insights into substrate recognition
    Wu et al., Nature Struct Mol Biol, 2015, 22, 1016-1022

 

Dr Liang Wu

York Research Database link

Find out more:
ORCID logohttps://orcid.org/0000-0003-0294-7065