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A photo of Prof HO Shu Leong
Prof HO Shu Leong
Henry G Leong Professor of Neurology
MD(Wales), FRCP(Edin, Lon, Glasg), FHKCP, FHKAM
an email logo slho@hku.hk
a telephone logo 2255-3315
a fax logo 2974-1171

Biography

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 Profile

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-B), 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.
Dr mak Research Photo
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.
Dr mak Research Photo
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.

Selected Publications

  1. Liu HF, Lu S, HO PWL, Tse HM, Pang SYY, Kung MHW, Ho JWM, Ramsden DB, Zhou ZJ*, Ho SL*. (2014) LRRK2 R1441G mice are more liable to dopamine depletion and locomotor inactivity. Annals of Clinical and Translational Neurology. In press.
  2. Ho PWL, Tse HM, So DHF, Ho JWM, Liu HF, Kung MHW, Ramsden DB, Ho SL*. (2013). Assessment of cellular estrogenic activity based on estrogen receptor-mediated reduction of soluble-form catechol-O-methyltransferase (COMT) expression in an ELISA-based system. PloS One. 8(9):e74065. doi: 10.1371/journal.pone.0074065.
  3. Ho PWL, Ho JWM, Tse HM, So DH, Yiu DC, Liu HF, Chan KH, Kung MH, Ramsden DB, Ho SL*. (2012) Uncoupling protein-4 (UCP4) increases ATP supply by interacting with mitochondrial Complex II in neuroblastoma cells. PLoS One. 2012;7(2):e32810.
  4. Ho JWM, Ho PWL, Liu HF, So HF, Chan KH, Tse MT, Kung HW, Ramsden DB, Ho SL*. (2012) UCP4 is a target effector of the NF-κB c-Rel prosurvival pathway against oxidative stress. Free Radic Biol Med. 53(2):383-94.
  5. Kwok KH, Ho PWL, Chu ACY, Ho JWM, Liu HF, Zhang WY, Xuan G, Chan KH, Kung MHW, Ramsden DB, Ho SL*. (2010) Mitochondrial UCP5 is neuroprotective by preserving mitochondrial membrane potential, ATP levels, and reducing oxidative stress in MPP+ and dopamine toxicity. Free Radic Biol Med. 49(6): 1023-35.
  6. Ho JWM, Ho PWL, Zhang WY, Liu HF, Kwok KH, Xuan G, Chan KH, Kung MHW, Ramsden DB, Ho SL*. (2010) Transcriptional regulation of UCP4 by NF-kappaB and its role in mediating protection against MPP+ toxicity. Free Radic Biol Med. 49 (2):192-204.
  7. Chu AC, Ho PW, Kwok KH, Ho JW, Chan KH, Liu HF, Kung MH, Ramsden DB, Ho SL*. (2009) Mitochondrial UCP4 attenuates MPP(+)- and dopamine-induced oxidative stress, mitochondrial depolarization, and ATP deficiency in neurons and is interlinked with UCP2 expression. Free Radic Biol Med. 46(6):810-20.
  8. Ho PWL, Garner CE, Ho JWM, Leung KC, Kwok KHH, Chu ACY, Kung MHW, Burka LT, Ramsden DB, Ho SL*. (2008) Estrogenic phenol and catechol metabolites of PCBs downregulate catechol-O-methyltransferase via the estrogen receptor: potential contribution to cancer risk. Current Drug Metabolism. 9(4):304-9.
  9. Tsang KL, Ho SL*, Lo SK. (2000) Estrogen improves motor disability in parkinsonian postmenopausal women with motor fluctuations. Neurology;54(12):2292-8.
  10. Xie T, Ho SL*, Ramsden DB. (1999) Characterization and implications of estrogenic down-regulation of human catechol-O-methyltransferase gene transcription. Molecular Pharmacology. 56(1):31-38.

Key Offices

  • Founding Director & Chairperson, Hong Kong Parkinson's Disease Foundation (2002 to date).
  • Chairperson, Advisory Committee, Dept of Rehabilitation Sciences, Polytechnic University, Hong Kong (2014 to date)
  • Member, Board of Governors, Matilda International Hospital (2005 to date),
  • Panel of Assessors, Hong Kong Medical Council (2007 to date).
  • Member, International Relations Subcommittee, American Academy of Neurology (2010 to date)
  • Member, International Executive Committee, Movement Disorder Society (2005 -2009)
  • Treasurer, Asian-Oceania Section (AOS), Movement Disorder Society (2005-2006)

Editorial Board Memberships

  • Clinical Neuropharmacology, Editorial Board Member (2006-2008), Associate Editor, (2008 to date)
  • Brain and Behavior, Editorial Board Member (2011 to date)
  • Translational Neurodegeneration, Editorial Board Member (2011 to date)

Patents

Human catechol-O-methyltransferase (COMT) assay. Listed inventors: PWL Ho, DB Ramsden, SL Ho.
  1. US patent publication no. US 2010/0081147 A1
  2. China patent publication no. CN 102203119 A
  3. European patent granted on 23rd October 2013; patent no. 2328909