Neurodegeneration Research Laboratory

​

Kah-Leong Lim, Ph. D

Visiting Lead (Strategic Alliances), National Neuroscience Institute (NNI)
Professor and Vice Dean (Research), Lee Kong Chian School of Medicine, Nanyang Technological University
Research Director (Biomedical and Life Sciences), President’s Office, Nanyang Technological University
Co-director, NTU-RIKEN Joint Centre
Visiting Professor, Department of Brain Science, Imperial College London, United Kingdom
Visiting Professor, Shanxi Medical University, China

Contact Information

Neurodegeneration Research Laboratory
National Neuroscience Institute
11 Jalan Tan Tock Seng, Singapore 308433
Tel: (65) 6357 7632 (Lab)
Fax: (65) 6256 9178

The NNI Team

• Ms Eugenia TE Hong, B.Sc. (Laboratory Manager)
• Dr Grace Lim Gui Yin, Ph.D. (Senior Research Fellow)
• Ms Choong Huey Ching, M.Sc. (Research Associate)
• Ms Wang Ziyin, B.Sc. (Hons) (Research Officer)
• Dr. Ren Mengda, Ph.D. (Research Fellow) – seconded from LKC
• Dr. Willcyn Tang, Ph.D. (Research Fellow) – seconded from LKC
• Ms Lim Boon Keng Stacey (Laboratory Technician) – seconded from LKC

Overview of Laboratory

The long term primary goal of my lab is to elucidate the molecular events underlying major neurodegenerative diseases, particularly in Parkinson Disease (PD), with the view to develop novel therapies aimed at effectively treating these debilitating disorders. We adopt a multi-pronged approach, including the use of different disease models, as well as a multidisciplinary approach (including collaborations with chemists and engineers), to achieve our objectives. To realise this goal progressively, our research work focuses on achieving the following inter-related objectives:

1. MECHANISMS – To identify and characterise key players/events that contribute to PD pathogenesis
2. MODELS – To generate reliable preclinical models of PD that would facilitate drug discovery efforts
3. MARKERS – To generate selective biomarker probes for disease diagnosis and monitoring
4. MEDICINE – To develop therapeutic strategies based on the knowledge gleaned from our research work

Science in the Hospital - Reversing Parkinson’s Damage: https://www.youtube.com/watch?v=G6miix6WH4w

Selected Publications

Selected (from >100 publications) (Total citations>20,000; h-index 53): https://scholar.google.com.au/citations?user=P9vYI5QAAAAJ&hl=en

Parkinson & Related Neurodegenerative Diseases

1. Lin, C., Yan, J., Kapur, M.D., Norris, K.L., Hseih, C.,  Lai, C.H., Vitale, N., Lim, K.L., Guan, Z.Q., Chi, J., Yang, W.Y., Yao, T.P. (2022) Parkin coordinates mitochondrial lipid remodeling to execute mitophagy. EMBO Reports (In press) (2022) (BioRxiv 2020.02.28.970210) (IF: 8.807)
2. Peng B, Hao S, Tong Z, Bai H, Pan S, Lim, K.L., Li L, Voelcker NH, Huang W (2022) Blood–brain barrier (BBB)-on-a-chip: a promising breakthrough in brain disease research. Lab on a Chip, 2022,22, 3579-3602 (IF: 7.517)
3. Selvaraji, S., Efthymios, M., Foo, R.S.Y., Fann, D.Y., Lai, M.K.P., Chen, C.L.H., Lim, K.L., Arumugam, T.V. (2022) Time-restricted feeding modulates the DNA methylation landscape, attenuates hallmark neuropathology and cognitive impairment in a mouse model of vascular dementia. Theranostics Mar 21;12(7):3007-3023 (IF: 11.56)
4. Xu, J., Du, W., Zhao, Y., Lim, K.L. Lu, L., Zhang, C.W. (2022) Mitochondria targeting drugs for neurodegenerative diseases-design, mechanism and application. Acta Pharmaceutica Sinica B. 12 (6): 2778-2789 (2022) (IF: 11.413)
5. Hang, L.T., Goh, G.W.Y., Wang, Z.Y., Foo, A.S.C., Choong, H.C., Thundyil, J., Xu, S., Lam, K.P., Lim, K.L. (2021) Conditional disruption of AMP kinase in dopaminergic neurons promotes Parkinson’s disease-associated phenotypes in vivo. Neurobiology of Disease 161:105560 (IF: 5.227)
6. Baik S.H., Selvaraji, S., Fann, D., Jo, D.G., Herr, D., Lai, M.K.P., Chen, C.L.H., Drummond, G.R., Lim, K.L., Sobey, C., Arumugam, T.V. (2021) Hippocampal transcriptome profiling reveals common disease pathways in chronic hypoperfusion and ageing. Aging (Albany NY) Jun 1;13(11):14651-14674 (IF: 5.682)
7. Yang, N., Liu, X., Wang, X., Jiang, R., Yuan, N., Wang, J., Zhang, C.W., Lim, K.L.*, Lu, L*. (*co-corresponding) (2021) Activation of Autophagy ameliorates age-related neurogenesis decline and neurodysfunction in adult mice. Stem Cell Reviews and Reports Feb;18(2):626-641 (IF: 6.43)
8. Jo, J., Yang, L., Tran, H., Yu, W., Yang, L., Sun, A., Chang, Y.Y., Jung, B.C., Lee, S.J., Saw, T.Y, Xiao, B., Khoo, A.T.T., Yaw, L.P., Xie, J.J., Lokman, H., Ong, W.Y., Lim, G.Y., Lim, K.L.*, Tan, E.K.*, Ng, H.H.*, Je, S*. (*co-corresponding) (2021) Lewy-body like Inclusions in Human Midbrain Organoid Carrying Glucocerebrosidase and Alpha Synuclein mutations. Annals of Neurology (IF:10.42)
9. Teh, B., Bansal, A., Chai, C., Toh, T.B., Jappy Tucker, R.A., Gammad, G.G.L., Yeo, Y., Lei, Z., Zheng, X., Feng, Y., Ho, J., Bolem, N., Wu, B.C., Gnanasammandhan, M.K., Hooi, L., Dawe, G.S., Libedinsky, C., Ong, W.Y., Halliwell, B., Chow, E.K.H., Lim, K.L.*, Zhang, Y.*, Kennedy, B*. (*co-corresponding) (2020) Flexi-PEGDA Upconversion Implant for Wireless Brain Photodynamic Therapy. Advanced Materials (IF: 30.85)
10. Rajan, S., Jang, Y., Kim, C., Kim, W., Toh, H.T., Jeon, J., Song, B., Maqueda, A.S., Lescar, J., Yoo, Y., Beldar, S., Ye, H., Kang, C., Liu, X., Feitosa, M., Kim, Y., Hwang, D., Goh, G., Lim, K.L., Park, H.M, Lee, C.H., Oh, S.F., Petsko, G., Yoon, H.S., Kim, K.S. (2020) PGE1 and PGA1 bind to Nurr1 and activate its transcriptional function. Nature Chemical Biology  (IF:15.04)
11. Ranjan, V.D., Qiu, L., Lee, J.W., Chen, X.L., Jang, S.E., Chai, C., Lim, K.L., Tan, E.K., Zhang, Y., Huang, W.M., Zeng, L. (2020) A microfiber scaffold-based 3D in vitro human neuronal culture model of Alzheimer's disease. Biomaterials Science Sep 7;8(17):4861-4874 (IF: 6.183)
12. Sun, A.X., Yuan, Q., Fukuda, M., Yu, W., Yan, H.D., Lim, G.G.Y., Nai, H.H., D'Agostino G.A., Tran, H., Itahana, Y., Wang, D., Lokman, H., Itahana, K., Lim, S.W.L., Tang, J., Cook, S.A., Rackham, Lim, C.T., Tan, E.K., Ng, H.H., Lim, K.L., Jiang, Y., Je, S. (2019) Potassium channel dysfunction in human neuronal models of Angelman syndrome. Science (IF: 47.73)
13. Kim, J., Selvaraji, S., Kang, S.W., Lee, W.T., Chen, L.C., Choi, H., Koo, E.H., Jo, D., Lim, K.L., Lim, Y.A., Arumugam, T.V. (2019) Cerebral transcriptome analysis reveals age-dependent progression of neuroinflammation in P301S mutant tau transgenic male mice. Brain, Behavior and Immunity Apr 11. pii: S0889-1591(18)30842-0 PMID: 30980950 (IF: 6.130)
14. Wang L, Cho YL, Tang Y, Wang J, Park JE, Wu Y, Wang C, Tong Y, Chawla R, Zhang J, Shi Y, Deng S, Lu G, Wu Y, Tan HW, Pawijit P, Lim GG, Chan HY, Zhang J, Fang L, Yu H, Liou YC, Karthik M, Bay BH, Lim KL, Sze SK, Yap CT, Shen HM. (2018) PTEN-L is a novel protein phosphatase for ubiquitin dephosphorylation to inhibit PINK1-Parkin-mediated mitophagy. Cell Research (IF: 25.62)
15. Ng, C.H., Basil, A.H., Hang, L.T., Tan, R., O’Neill S., Zhang, X.D., Yu, F., Lim, K.L. (2017) Genetic or pharmacological activation of the Drosophila PGC-1α ortholog rescues the disease phenotypes of genetic models of Parkinson’s disease. Neurobiology of Aging (IF:4.673)
16. Lim, G.G.Y., Lim, K.L. (2017) Parkin-Independent Mitophagy – FKBP8 comes to play. EMBO Reports (Invited Editorial) (IF:8.8)
17. Nucifora, F.C., Nucifora, L.G., Ng, C.H., Arbez, N., Guo, Y., Roby, E., Shani, V., Engelender, S., Wei, D., Wang, X.F., Li, T., Moore DJ, Pletnikova, O., Troncoso, J., Sawa, A., Dawson, T.M., Smith, W., Lim, K.L., Ross, C.A. (2016) Ubiqutination via K27 and K29 chains signals aggregation and neuronal protection of LRRK2 by WSB1. Nature Communications 7: 11792.
18. Lim, G.G., Chua, D.S.K., Basil, A.H., Chan, H.Y., Chai, C., Arumugam, T., Lim, K.L. (2015) Cytosolic PTEN-induced putative kinase 1 is stabilized by NF-κB pathway and promotes non-selective mitophagy Journal of Biological Chemistry 290(27):16882-93.
19. Li, L., Zhang C.W., P., Chen G.Y.J., Zhu, B., Y.W., Chai. C., Xu, Q., Tan, E.K., Kung, S.K.P., Lim, K.L.*, Yao, S.Q.* (2014) A Two-Photon Small Molecule Enzymatic Probe for Specific and Sensitive Detection of Monoamine Oxidase B Activity in Parkinson’s Disease Models. Nature Communications 13;5:3276 (*co-corresponding).