Translational Therapeutics Laboratory

​Zhou Zhidong, MD, Ph.D
Associate Clinician Scientist, Translational Therapeutics Laboratory
Adjunct Assistant Professor at Duke-NUS Medical School

Contact Information

Translational Therapeutics Laboratory
Duke-NUS Graduate Medical School, NBD, Level 6
8 College Road, Singapore 169857
Tel: (65) 6601 3742 (Office)
Fex: (65) 6256 9178
Email: zhidong_zhou@nni.com.sg

The Team

Xie Shao Ping, MSc (Research Fellow)
Sushmitha Sathiyamoorthy, MSc (Research Fellow)
Saw Wuan Ting, MSc (Research Fellow)
Heidi Pek Hup Chua, BSc Hons (Senior Research Assistant)

Grant Support

NMRC NIG and NMRC TA awards
SingHealth Foundation Grant

Overview

Our laboratory’s interests lie in identification and verification of novel key molecular targets, signaling pathways or neuro-protective agents relevant to pathogenesis and therapy of debilitating human neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson disease (PD) and multiple sclerosis.

To achieve it, cutting-edged high throughput screening works are being performed in the lab. First, the in vitro high throughput proteomics screening plus immuno-precipitation protocols as well as cellular and molecular techniques are utilized to search and identify new key molecular targets or novel signaling pathways relevant to pathogenesis and therapy in human neurodegenerative diseases. Second, in vitro high throughput chemical library screening is being performed to identify new neuro-protective agents to modulate identified new molecular targets or signaling pathways for future clinical drugs developments. Findings from in vitro identification of new targets or new neuron protective agents will be further strengthened by our in vivo verification studies in our environmental or genetic Drosophila or mice disease models. Third, direct in vivo high throughput screening using our newly established toxic in vivo Drosophila models is used to search for new dopamine neuron degeneration relevant genes or new potential anti-PD drugs for PD pathogenesis and therapy.

These researches are conducted in close collaboration with Professor Tan Eng King, Research Director, NNI and Senior Consultant, Department of Neurology, NNI (Singapore General Hospital. campus) to emphasize potential clinical implications and applications of our findings. Our works will not only advance our understanding of the pathogenesis of human degenerative disorders, but also can benefit patients via contribution of new therapeutic agents or strategies against human neuron degenerative diseases in the future.

Selected Publications

1. Angeles DC, Ho P, Chua LL, Wang C, Yap YW, Ng C, Zhou ZD, Lim KL, Wszolek ZK, Wang H, and Tan EK. Thiol-peroxidases ameliorate LRRK2 mutant-induced mitochondrial and dopaminergic neuronal degeneration in Drosophila. Human Molecular Genetics (2014) June 15; 23:3157-65.
2. Z.D. Zhou, F S Refai, S P Xie, S H Ng, C H Shan Chan, P H G Hoe, X D Zhang, T M Lim, E K Tan. Mutant PINK1 up-regulates tyrosine hydroxylase and dopamine levels leading to vulnerability of dopaminergic neurons. Free Radical Biology & Medicine, 2014. 68:220-33.
3. Z.D. Zhou, C. H. S. chan, Z. C. Xiao and E. K. Tan, “Ring finger protein 146 / iduna is a Poly(ADP-ribose) polymer binding and PARsylation dependent E3 ubiquitin ligase”. Cell Adhension & Migration. 2011. 5(6):463-71.
4. Z.D. Zhou, Sushmitha Sathiyamoorthy and E. K. Tan, LINGO-1 and neurodegeneration: pathophysiologic clues for essential tremor? Tremor and Other Hyperkinetic Movements (TOHM). 2012.
5. Z.D. Zhou, C. H. S. chan, Z. C. Xiao and E. K. Tan, “The Roles of Amyloid Precursor Protein (APP) in Neurogenesis, Implications to Pathogenesis and Therapy of Alzheimer's Disease (AD)”. Cell Adhension & Migration. 2011 Jul 1;5(4):280-92.
6. Z.D. Zhou, Y.H. Lan, E.K. Tan and T.M. Lim, “Iron species-mediated dopamine oxidation, proteasome inhibition, and dopaminergic cell demise: implications for iron-related dopaminergic neuron degeneration.” Free Radical Biology & Medicine, 2010 Dec 15;49(12):1856-71.
7. Z.D. Zhou, Z.Y.Kerk, G.G. Xiong and T. M. Lim, “Dopamine auto-oxidation aggravates non-apoptotic cell death induced by overexpression of human A53T mutant alpha-synuclein in dopaminergic PC12 cells”. Journal of Neurochemistry, 108 (2009) 601-610.
8. Z.D. Zhou, B.P. Yap, A.Y.T. Gung, S.M. Leong, S. T. Ang and T.M. Lim, “Dopamine-related and caspase-independent apoptosis in dopaminergic neurons induced by overexpression of human wild type or mutant α-synuclein,” Experimental Cell Research, 312 (2006) 156-170.
9. Z.D. Zhou, Udhaya. Kumari, Z.C. Xiao and E. K. Tan, “Notch as a Molecular Switch in Neural Stem Cells (NSC),” IUBMB life, 62 (2010), 618-623.
10. Z.D. Zhou, T.M. Lim, “Role of glutathione (GSH) on dopamine (DA) oxidation, studied by improved tandem HPLC procedures plus ESI-MS.” Neurochem Research, 34 (2009) 316-326.
11. Z.D. Zhou, T.M. Lim, “Glutathione conjugates with dopamine-derived quinones to form reactive or non-reactive glutathione-conjugates, implications to dopaminergic neuron degeneration.” Neurochem Research, 2010 Nov;35(11):1805-18.
12. Z.D. Zhou, Z.Y. Kerk and T.M. Lim, “Endogenous dopamine (DA) renders dopaminergic cells vulnerable to challenge of proteasome inhibitor MG132” Free Radical Research, 42 (2008) 456-466.
13. Z.D. Zhou, T.M. Lim, “Dopamine (DA) induced irreversible proteasome inhibition via DA derived quinones.” Free Radical Research, 43 (2009), 417-430.