Obtained MB BCh from University of Wales College of Medicine, Cardiff, UK (1986). General medical rotations in Coventry, Manchester and Birmingham (1987-89), with MRCP (1989). Trained in Neurology in different hospitals in Birmingham with Clinical Research Fellowship at the University of Birmingham, UK (1989-1994). Obtained MD (Wales) in 1995 from exploring the role of xenobiotic enzymes including mono-oxidase-B (MAOB) in Parkinson’s disease. Joined HKU in 1994 as a Lecturer, appointed as Associate Professor in 1997, and as Clinical Professor in 2006. Awarded FHKCP in 1995, FHKAM in 1996, and FRCP of the three Royal Colleges in 1998, 1999 and 2000 respectively. Endowed with the Henry G Leong Professorship in Neurology in 2008. Chief of Division (Academic & Clinical Services) in Neurology in HKU and Queen Mary Hospital since 1997.

Research work

I lead a research team in HKU focusing mainly on Parkinson’s disease (PD), its etiology, pathogenesis and exploring therapeutic methods to modify these processes. Our earlier research described how a ubiquitous xenobiotic enzyme, catechol-O-methyltransferase (COMT) provided the link between the effects of estrogen and PD. This project delivered tangible materials including human COMT antibodies and a patented COMT ELISA assay containing a unique synthetic 18 amino acid polypeptide protein tag. This enzyme assay can quantify the estrogenic effects of environmental pollutants, such as PCBs and plasticizers linked to cancer and neurodegeneration. It is being used by our collaborators in environmental sciences to study the extent and effects of marine pollution in Hong Kong on human health.

In a later project, we focused on mitochondrial dysfunction, an important pathogenic process involved in PD. We described and elucidated some of the neuroprotective mechanisms of mitochondrial neuronal uncoupling proteins (UCPs) in experimental models of PD. We have developed methods and materials including antibodies to human neuronal uncoupling proteins (UCP4 and 5). Our studies uncovered a novel link between UCPs and nuclear-factor kappa-B (NF-kB), and more specifically the c-Rel pro-survival pathway, which can be a potential therapeutic target in PD. In parallel studies, we described the beneficial effects of leptin (a regulator of metabolism) on neuronal survival being mediated via UCP2, supporting a link between metabolic pathways and pathogenic processes in PD. We also elucidated how UCP4 interacted with mitochondrial Complex II to preserve ATP synthesis under cellular stress.

In our latest project, we developed a unique colony of an experimental mouse model with a leucine-rich repeat kinase-2 (LRRK2) knockin mutation (C57BL/6N background) based on the mutation found in familial PD. We found abnormal locomotor behavior with impaired recovery in young mutant mice associated with defective synaptosomal dopamine uptake at their striatal pre-synaptic nerve terminals compared with wildtype controls following reserpine-induced dopamine depletion. Our current work focuses on pathogenic mechanisms involved in LRRK2-related PD. Parallel studies are being conducted to explore genetic-environmental interactions in these pathogenic processes. One key aim is to deliver unique materials in unraveling the pathogenic processes of PD and develop therapeutic methods to alleviate them.

Over the past 15 years, we have been documenting and collecting biological samples with various neurodegenerative disorders, including PD, sporadic amyotrophic lateral sclerosis (ALS), familial ALS associated with SOD1, spinocerebellar ataxias and hereditary sensory motor neuropathies, with ongoing collaborative metabonomics and neuroimaging studies to explore for biomarkers and neuroimaging in PD and ALS.