Using in vitro and in vivo assays established in the lab, combining Alzheimer’s disease with Parkinson’s disease transgenic mouse models; using anti-sense RNA technology, retroviral and lentiviral strategies, together with in utero electroporation, stereotaxic injections and animal behaviour tests, we aim to:
• Unravel molecular mechanism underlying microRNA-mediated neurogenesis in neural developmental disorders: congenital developmental symptoms and autisum
• Identify microRNAs signature as a biomarker in early onset of dementia
• Establish neuropathophysiology cross-talk between Alzheimer’s disease and Parkinson’s disease
• Explore the novel stem cells therapy in Parkinson’s disease
Selected Publications:
Chen Z, Zhang W, Chua LL, Chai C, Li R, Lin L, Cao Z, Angeles D. C, Stanton W. L, Peng J, Zhou ZD, Lim KL, Zeng L,* Tan EK* (2017) Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson’s disease. Sci Signal. 2017 Jul 18;10(488). pii: eaam6790. doi: 10.1126/scisignal.aam6790.
Chen Z, Cao Z, Zhang W, Gu M, Zhou ZD, Li B, Li J, Tan EK, Zeng L (2017) LRRK2 Interacts with ATM and Regulates Mdm2-p53 Cell Proliferation Axis in Response to Genotoxic Stress. Hum Mol Genet. 2017 Nov 15;26(22):4494-4505. doi: 10.1093/hmg/ddx337. PMID: 28973420.
Qiu, L., Liao, M. C., Chen, A. K., Wei, S., Xie, S., Reuveny, S., Zhou, Z. D., Walter, H., Tan, E.K. Oh, S. K.W., Zeng, L (2017) Immature midbrain dopaminergic neurons derived from floor-plate method improve cell transplantation therapy efficacy for Parkinson’s disease. Stem Cells Transl Med. 2017 Sep;6(9):1803-1814. doi: 10.1002/sctm.16-0470. Epub 2017 Jun 26.
Ma, D., Ng, SH., Zeng, L., Zhao, Y., Tan EK (2017) Generation of a human induced pluripotent stem cell (iPSC) line carrying the Parkinson's disease linked LRRK2 variant S1647T. Stem Cell Res. 18:54-56. doi: 10.1016/j.scr.2016.12.010. Epub 2016 Dec 9.
Tan, YJ., Ng, ASL., Vipin, A., Lim, JKW., Chander, RJ., Ji, F., Qiu, Y., Ting, SKS., Hameed, S., Lee, TS., Zeng, L., Kandiah, N., Zhou J (2017) Higher Peripheral TREM2 mRNA Levels Relate to Cognitive Deficits and Hippocampal Atrophy in Alzheimer's Disease and Amnestic Mild Cognitive Impairment. J Alzheimers Dis. doi: 10.3233/JAD-161277.
Zhang, W., Kim, PJ., Chen, Z., Lokman, H., Qiu, L., Zhang, K., Rozen, S.G., Tan, E.K., Je, HS*., Zeng, L* (2016) MicroRNA-128 Regulates the Proliferation and Neurogenesis of Neural Precursors by Targeting Pericentriolar Material 1 (PCM1) in the Developing Neocortex. eLife. doi: 10.7554/eLife.11324.
Qiu, L., Ng, G., Tan, E.K., Liao, P., Kandiah, N., Zeng, L (2016) Chronic cerebral hypoperfusion enhances Tau hyperphosphorylation and reduces autophagy in Alzheimer’s disease mice. Sci Rep. 6:23964. doi: 10.1038/srep23964.
Qiu, L., Lim, Y.M., Chen, A.K., Reuveny, S., Oh, S.K., Tan, E.K., Zeng, L (2016) Microcarrier-Expanded Neural Progenitor Cells Can Survive, Differentiate, and Innervate Host Neurons Better When Transplanted as Aggregates. Cell transplantation 25, 1343-1357.
Zhou, ZD., Xie, SP., Sathiyamoorthy, S., Saw, WT., Sing, TY., Ng, SH., Chua, HP., Tang, AM., Shaffra, F., Zeng, L., Wang, H., Ho, PG., Lai, MK., Angeles, DC., Lim, TM., Tan, E.K (2015). F-box protein 7 mutations promote protein aggregation in mitochondria and inhibit mitophagy. Hum Mol Genet. 15;24(22):6314-30.
Zhang, W., Thevapriya, S., Kim, P.J., Yu, W., Je, HS., Tan, E.K., Zeng, L (2014) Amyloid precursor protein regulates neurogenesis by antagonizing miR-574-5p in the developing cerebral cortex. Nat. Commun. 5:3330. doi:10.1038/ncomms4330.