Tan, Eng King

Research Interests:

Dr Tan research interests focus on clinical and translational research in Parkinson's Disease (PD), essential tremor (ET), Alzheimer's disease (AD), spinocerebellar ataxias (SCA), restless legs syndrome (RLS) and related neurodegenerative disorders.

Clinical Research

1. Clinical studies aimed at evaluating clinical and genetic risk factors of disease-related, and drug-related complications in the above mentioned disorders. His group also conducts health-related quality of life research to improve the clinical care for these patients.
2. Pharmaceutical trials aimed at improving clinical outcome in patients with neurodegenerative disorders.
3. Imaging studies using advanced MR techniques (such as Diffusion Tensor Imaging) to evaluate and differentiate different neurodegenerative disorders.

Genetic Research

His group is investigating the intersection between genomics and cell biology, supported by major technical platforms of high throughput sequencing, bioinformatics, proteomics and expression array technologies in our research institutions. Specifically, his group hopes to elucidate genetic risk factors and gene-environment interaction in large population-based studies for neurodegenerative disorders, and to investigate their functional significance in cellular models. The candidate gene selection targets at different cellular pathways that are responsible for cell integrity, function and survival and also those which modulate either individual's exposure to environmental agents or cellular response to such exposure. Ascertainment of a detailed environmental and lifestyle risk factor information of study subjects provides a unique opportunity to explore the gene-environment interaction. The work is supported by a large gene bank of patients with neurodegenerative disorders. His group collaborates actively with investigators from USA, Europe and Asia.

Proteomic Research

His group is also working on unraveling the pathophysiological mechanism underpinning the role of two important proteins, LRRK2 and PINK1, in the pathogenesis of PD. Using yeast-2-hybrid, mass spectrometry and other molecular methods, his group has identified potential interactors of these two proteins. The group is in the process of characterizing the exact mechanism of interaction between these proteins and determines how they fit into the neurodegenerative pathways that would lead to protein accumulation, impaired proteasomal and mitochondrial dysfunction, and nitrosative and oxidative stress. Specifically the group hopes to decipher how dysregulation of the kinase activity and altered signaling pathway could lead to neuronal cell death and identify potential therapeutic strategies to slow down the disease process. Work is currently conducted in human dopaminergic cell lines and in human post-mortem brain samples. Collaborators include investigators from USA and Japan.

Professional Interests

1. Clinical care: Provides specialist care for patients with neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, essential tremor, spinocerebellar ataxias, and other movement disorders.
2. Academic work: Currently associate editor of three journals, including two international journals, European Journal of Neurology (European Federation of Neurological Societies) and Parkinsonism Related Disorders (World Federation of Neurology), and our medical journal, Annals, Academy of Singapore.
3. Educational Work: Currently in the Executive Committee, Asian Oceanic International Movement Disorders Society, and Scientific Issues Committee, International Movement Disorders Society and member of Ministry of Health SAB Research Committee.
4. Training: Provides training for clinical fellows and specialty training for doctors from Asia, and laboratory training for undergraduates and postgraduates from various tertiary institutions.

Selected Publications:

Lu YW, Tan EK. Molecular biology changes associated with LRRK2 mutations in Parkinson's disease. J Neuroscience Res. 2008;86(9):1895-901.

Tan EK, Tang M, Tan LC, et al. Lrrk2 R1628P in non-Chinese Asian races. Ann Neurol. 2008;64(4):472-3.

Tan EK, Chua E, Fook-Chong SM, Teo YY, Yuen Y, Tan L, Zhao Y. Association between caffeine intake and risk of Parkinson's disease among fast and slow metabolizers. Pharmacogenetics Genomics. 2007;17(11):1001-5

Tan EK, Lee J, Chen CP, Teo YY, Zhao Y, Lee WL. SORL1 haplotypes modulate risk of Alzheimer's disease. Neurobiology of Aging. 2008

Tan EK, Chan LL. Neurovascular compression syndromes and hypertension: clinical relevance. Nature Clinical Practice Neurology. 2007;3(8):416-7

Tan EK, Skipper L. Pathogenic mutations in Parkinson's disease. Human Mutation 2007;28(7):641-53.

Maraganore DM, de Andrade M, Elbaz A, Farrer MJ, Ioannidis JP, Kruger R, Rocca WA, Schneider NK, Lesnick TG, Lincoln SJ, Hulihan MM, Aasly JO, Ashizawa T, Chartier-Harlin MC, Checkoway H, Ferrarese C, Hadjigeorgiou G, Hattori N, Kawakami H, Lambert JC, Lynch T, Mellick GD, Papapetropoulos S, Parsian A, Quattrone A, Riess O, Tan EK, Van Broeckhoven. Collaborative analysis of alpha-synuclein gene promoter variability and Parkinson disease. JAMA. 2006;296(6):661-70.

Skipper L, Tan EK, Liu JJ. Comprehensive evaluation of common genetic variation within LRRK2 reveals evidence for association with sporadic Parkinson's disease. Human Molecular Genetics. 2005;14(23):3549-56.

Tan EK, Lo YL, Chan LL. Orthostatic tremor and Graves disease. Neurology 2008;70(16 Pt 2):1497-8.

Tan EK, Zhao Y, Skipper L, et al. The LRRK2 Gly2385Arg variant is associated with Parkinson's disease: genetic and functional evidence. Human Genetics. 2007;120(6):857-63.