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Neural Stem Cell Research Laboratory


ZENG LI, Ph.D.

1996 - University of Glasgow, U.K. (Neuroscience & Molecular Pharmacology Program)
2009 - Principal Investigator, Neural Stem Cell Research Laboratory
Adjunct Assistant Professor, Neuroscience & Behavioural Disorders Program, DukeE-NUS, GMS

Contact Information

Neural Stem Cell Research Laboratory
National Neuroscience Institute
11 Jalan Tan Tock Seng, Singapore 308433
Tel: (65) 6357 7515 (Office) / (65) 6357 7505 (Lab)
Fax: (65) 6256 9178
Email: Li_ZENG@nni.com.sg

The Team

  • Dr Zhang Wei
  • Dr Chen Zhong-Can
  • Dr Qiu Li-Feng
  • Dr Zeng Xiao-Xia
  • Ms Gu Xin-Xia
  • Ms Christina Lim (Lab Manager)
  • Mr Ranjan Vivek Damodar (NTU Student)

Overview

Alzheimer’s disease (AD) is the most common neurodegenerative disease seen in Singapore. Recent evidences suggested that impaired neurogenesis might contribute to cognitive dysfunction observed in AD. Amyloid precursor protein (APP) is a type I transmembrane glycoprotein proteolytically processed to release Aβ (amyloid beta), a pathological hallmark of AD. Although, this protein is expressed throughout the developing and mature brain; the roles of APP in neural development and neural stem cell function are not well established. microRNAs (miRNAs) are small noncoding RNA molecules that function in the transcriptional and post-transcriptional regulation of gene expression in a variety of organisms.

The role of miRNAs in neuronal development and neural stem cell function has been recently identified. Notably, dysregulated miRNAs have been implicated in AD. We aim to unravel the molecular mechanisms underlying APP-dependent miRNA-mediated neuronal differentiation in AD; working with clinician doctors at NNI, we aim to develop miRNAs as biomarkers for AD by detecting miRNAs level changes in cerebrospinal fluid (CSF), and peripheral blood mononuclear cells (PBMCs) from AD subjects, compared to the healthy individuals. Our research will advance the understanding of miRNA regulatory pathway in association with impaired neurogenesis and cognitive dysfunction observed in AD. Importantly, our study will identify miRNAs as novel non-invasive diagnostic biomarkers, and help in developing miRNA-based therapeutics strategy in AD.

In addition, we have been collaborating with Professor Tan Eng King, Director of Research at NNI and a Clinician Scientist at the Department of Neurology (NNI-SGH campus), to incorporate genetically modified mice model of PD and neural stem cell/neuron cell cultures into our analysis to identify any potential pathogenic factors, substrates, miRNAs and their regulatory pathways at the molecular, cellular, network, and behavioral level. Mouse models are also being used to develop and evaluate novel treatment strategies. Their relevance is assessed through the comparative studies of humans and postmortem tissues to establish prospective collaboration with clinical programmes.

Selected Publications

  1. 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.
  2. 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. Accepted.
  3. 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. Accepted.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. Qiu, L., Zhang, W., Tan, E.K., Zeng, L (2014). Deciphering the Function and Regulation of microRNAs in Alzheimer's Disease and Parkinson's Disease. ACS Chem Neurosci. 15;5(10):884-94. doi: 10.1021/cn500149w.
  12. Lim, H.C., Xie, L., Zhang, W., Li, R., Chen, Z., Wu, G., Cui, S., Tan, E.K., Zeng L (2013) Ribosomal S6 Kinase 2 (RSK2) maintains genomic stability by activating the Atm/p53-dependent DNA damage pathway. PLoS One. 8(9):e74334. doi: 10.1371/journal.pone.0074334.
  13. Bichler Z, Lim HC, Zeng L, Tan EK. (2013) Non-motor and motor features in LRRK2 transgenic mice. PLoS One. 8(7):e70249. doi: 10.1371/journal.pone.0070249.
  14. Wang X*, Zeng L*, Wang J, Chau JF, Lai KP, Jia D, Poonepalli A, Hande MP, Liu H, He G, He L, Li B. (2011) A positive role for c-Abl in Atm and Atr activation in DNA damage response. Cell Death Differ. 18(1):5-15. *co-first authors.
  15. Lai KP, Leong WF, Chau JF, Jia D, Zeng L, Liu H, He L, Hao A, Zhang H, Meek D, Velagapudi C, Habib SL, Li B. (2010) S6K1 is a multifaceted regulator of Mdm2 that connects nutrient status and DNA damage response. EMBO J. 29(17):2994-3006.
  16. Ma QH, Futagawa T, Yang WL, Jiang XD, Zeng L, Takeda Y, Xu RX, Bagnard D, Schachner M, Furley AJ, Karagogeos D, Watanabe K, Dawe GS, Xiao ZC. (2008) A TAG1-APP signalling pathway through Fe65 negatively modulates neurogenesis. Nat Cell Biol. 10(3):283-94.
  17. Zeng L, Hu Y, Li B. (2005) Identification of TopBP1 as a c-Abl-interacting protein and a repressor for c-Abl expression. J Biol Chem. 280(32):29374-80.
  18. Nie DY, Zhou ZH, Ang BT, Teng FY, Xu G, Xiang T, Wang CY, Zeng L, Takeda Y, Xu TL, Ng YK, Faivre-Sarrailh C, Popko B, Ling EA, Schachner M, Watanabe K, Pallen CJ, Tang BL, Xiao ZC. (2003) Nogo-A at CNS paranodes is a ligand of Caspr: possible regulation of K(+) channel localization. EMBO J. 22(21):5666-78.
  19. Zeng L, Si X, Yu WP, Le HT, Ng KP, Teng RM, Ryan K, Wang DZ, Ponniah S, Pallen CJ. (2003) PTP alpha regulates integrin-stimulated FAK autophosphorylation and cytoskeletal rearrangement in cell spreading and migration. J Cell Biol. 160(1):137-46.