Skip Ribbon Commands
Skip to main content

Translational Therapeutics Laboratory

NNI Dr Zhou Zhidong.jpg

​Zhou Zhidong, MD, Ph.D
Clinician Scientist, Translational Therapeutics Laboratory
Assistant Professor, NBD, 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



Our translational studies focus on new therapeutic targets, biomarkers and neuroprotective pre-drugs for Parkinson's Disease and other neuron degenerative diseases. To achieve it, high throughput screening investigations combined with multi-disciplinary techniques, including gene-editing techniques, stem cell techniques, single cell sequencing and meta-analysis, 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 utilised to search and identify key therapeutic targets, biomarkers or signaling pathways relevant to human neurodegeneration.

Second, in vitro high throughput chemical library screening is being performed to identify neuroprotective compounds or pre-drugs targeting at key molecules or signaling pathways for Hit & Lead (H & L) drug developments.

Third, key therapeutic targets, biomarkers and promising pre-drugs identified from in vitro studies are being verified, validated and investigated in our multiple disease models, including environmental or transgenic C elegans, Drosophila, mice disease models as well as patient cells derived human neuron and brain organoid models. These researches are conducted in close collaboration with Professor Tan Eng King, Senior Consultant, Department of Neurology, NNI@SGH as well as other local and international researchers to emphasise clinical implications and applications of our findings to make allied victory.

Our works will not only advance our understanding of disease pathogenesis, but also benefit our patients via contributions of new therapeutic drugs, diagnostic biomarker and therapeutic strategies against human neurodegeneration.

Scheme 1. Illustration of the role of LRRK2-PINK1 on TH expression and DA synthesis in DA neurons
Under physiological conditions, LRRK2 and PINK1 form a functional balance to maintain normal TH expression and DA synthesis in DA neurons. LRRK2 promotes TH expression and DA generation, while PINK1 suppresses TH expression and DA generation. LRRK2 and PINK1 can regulate degradation of each other, thus a balance can be reached. When LRRK2 is mutated its kinase activity is increased, leading to up-regulated TH expression and increased DA generation. Increased LRRK2 kinase activity can facilitate PINK1 degradation, down regulate PINK1 level and suppress PINK1 function. This will lead to imbalance between LRRK2 and PINK1, contributing to increased TH expression, enhanced DA generation, aggravated DA oxidation and elevated DA relevant stress in DA neurons, promoting neurodegeneration. When PINK1 is mutated, kinase activity will be impaired causing LRRK2-PINK1 imbalance and disrupting TH-DA pathway, promoting DA neuron vulnerability and neurodegeneration.

Grant Support

  • SingHealth Duke-NUS Collaboration Pilot Grant
  • NMRC CS-IRG Grant.
  • MOH and NAM, HLCA Grant


Selected Publications in the Past Five Years

  1. Zhi-Wei Zhang, Hai Tao Tu, Zhi Dong Zhou, et al. APP Intracellular Domain Promotes Expression of LRRK2 Enabling a Feed-Forward Loop of Neurodegeneration in Parkinson’s Disease. Science Signaling. In press. IF: 9.517
  2. Zhi Dong Zhou, Joseph Jankovic, Tetsuo Ashizawa, and EK Tan Neurodegenerative diseases associated with non-coding CGG tandem repeat expansions, Nature Reviews Neurology. 2022. 18 (3), 145-157 IF: 42.0.
  3. Zhi Dong Zhou, Dennis Qing Wang, Eng-King Tan. The Role of Neurovascular Unit in Neurodegeneration. Frontiers in Cellular Neuroscience. 2022; 16: 870631. IF: 6.147
  4. H Liu, B Deng, Z Wu, H Zhou, Y Chen, G Weng, S Zhu, Zhi Dong Zhou. QEEG Indices Associated with Neuro-inflammatory and Metabolic Risk Factors: Potential Signatures of Dementia in Parkinson’s Disease. 2022. eClinicalMedicine. DOI: IF: 17.033.
  5. Zhi Dong Zhou & Eng King Tan. Oxidized nicotinamide adenine dinucleotide-dependent mitochondrial deacetylase sirtuin-3 as a potential therapeutic target of Parkinson’s Disease. Ageing Research Review. 2020. Sep;62:101107. IF: 10.616. *, Corresponding author
  6. Zhi Dong Zhou, et al. The therapeutic implications of tea polyphenols against dopamine (DA) neuron degeneration in Parkinson’s disease (PD). Cells. 2019; 8(8): 911. IF: 7.660, *, Corresponding author
  7. Zhi Dong Zhou, et al. Molecular targets for modulating the protein translation vital to proteostasis and neuron degeneration in Parkinson’s disease. Translational Neurodegeneration. 2019 Feb 4;8:6. IF: 9.883, *, Corresponding author
  8. Zhi Dong Zhou, Ji Chao Tristan Lee & Eng King Tan. Pathophysiological mechanisms linking F-box only protein 7 (FBXO7) and Parkinson’s disease (PD), Mutation Research/Reviews in Mutation Research 2018, 8: 72-78. IF: 7.015, *, Corresponding author
  9. Zhong Can Zhen. Zhi Dong Zhou, et al. LRRK2 Interacts with ATM and Regulates Mdm2-p53 Cell Proliferation Axis in Response to Genotoxic Stress. Human Molecular Genetics. 2017 Nov 15;26(22):4494-4505. IF: 6.150
  10. Zhi Dong Zhou & Eng King Tan. Iron Regulatory Protein (IRP)-Iron Responsive Element (IRE) Signaling Pathway in Human Neurodegenerative Diseases. Molecular Neurodegeneration, 2017 Oct 23;12(1):75. IF: 18.876 *, Corresponding author
  11. Bin Xiao, Xiao Deng, Grace Lim, Shaoping Xie, Zhi Dong Zhou, and et al. Superoxide drives progression of Parkin/PINK1-dependent mitophagy following translocation of Parkin to mitochondria. Cell death and Disease. 2017 Oct 12;8(10):e3097. IF: 8.79
  12. Lifeng Qiu, Zhi Dong Zhou, et al. Immature midbrain dopaminergic neurons derived from floor-plate method improve cell transplantation therapy efficacy for Parkinson’s disease. STEM CELLS Translational Medicine, 2017:1803-1814. IF: 7.65
  13. Zhong Can Chen, Zhi Dong Zhou, et al. Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson’s disease. Science Signaling. 2017 Jul 18;10(488). IF: 9.517
  14. Murni T, Wen RJ, Zhi Dong Zhou, et al. Varied pathological and therapeutic response effects associated with CHCHD2 mutant and risk variants. Human mutation, 2017 Apr 21. doi: 10.1002/humu.23234. IF: 4.878