I started my PhD project under the supervision of Professor Gideon Davies in the York Structural Biology Laboratory in September 2007.
My project subject was focused on the study of the catalytic mechanism of O-GlcNAc hydrolase (O-GlcNAcase) and the development of small molecular inhibitors as chemical probes of cellular function. During my PhD, I investigated a series of compounds representing various templates using a combination of enzymic kinetic, thermodynamic and X-ray crystallographic studies. For instance, we elucidated the coordinate of O-GlcNAcase catalyzed reaction using enzymes and compounds with tailored reactivity; developed a potent and selective O-GlcNAcase inhibitor (thiaMet-G) that could prevent phosphate damage to tau in the initiation of Alzheimer’s disease; proved STZ induced β-cell toxicity is not due to the irreversible inhibition of human O-GlcNAcase; and investigated the substrate binding distortion of seven-membered iminocyclitols. In 2010 I received the Chemistry Department Shell Poster Award.
Following my PhD I took up a research position at the Scripps Research Institute in the USA.