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Zeng Li, Ph.D.
Head and Principal Investigator
Neural Stem Cells Research Laboratory
National Neuroscience Institute
11 Jalan Tan Tock Seng
Singapore 308433
Tel: (65) 6357-7515
Fax: (65) 6256-9178
Email : Li_ZENG@nni.com.sg
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BIOGRAPHY
- Principal Investigator, National Neuroscience Institute, Singapore. (2009 - date)
- Research Scientist, Institute of Molecular and Cell Biology, Agency for Science, Technology and research, Singapore. (2002-2008)
- Research Fellow, Institute of Molecular and Cell Biology, National University of Singapore. (1997-2001)
- Ph.D. University of Glasgow, Scotland, UK. (1993-1996)
RESEARCH INTERESTS
Neurogenesis, which persists in the adult mammalian brain, may provide a basis for neuronal replacement therapy in neurodegenerative disease (NDD), like Alzheimer disease (AD). Despite intense investigations, no effective therapy is currently available to prevent the onset or to halt the progression of the neuronal cell loss. Therefore, in recent years research has mainly been focused on the mechanisms of endogenous repair process occurring in the adult brain. Our research interest however is to unravel the molecular basis of neurogenesis underlying the pathogenesis of the AD, particularly for the biological function of microRNAs (miRNA) which play the role in mediating the neural differentiation process. Dysregulated miRNAs have shown to be associated with pathogenesis of AD. Our ultimate goal is to identify miRNA and its targeted gene in mediating neurogenesis, and to help understanding the basis for impaired neurogenesis that may contribute to the cognitive dysfunction observed in the diseased brain. miRNAs has emerged as a powerful therapeutic tool for gene regulation due to its size, abundance, tissue specificity, and relative stability in plasma. The precise understanding of APP/Ab-miRNA-mRNA target relationships will be an absolute requirement for therapeutic effectiveness of the miRNA, and they might serve as the future therapeutic targets for the treatment of AD.
Recently, we have been collaborating with A/Prof Tan Eng King, 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 programs.
REPRESENTATIVE PUBLICATIONS
X. Wang*, L.Zeng*, J. Wang*, JF. Chau, KP. Lai, D. Jia, A. Poonepalli, MP. Hande, H. Liu, G. He, L. He, and B. Li "A positive role for c-Abl in Atm and Atr activation in DNA damage response". * Equally contributions. Cell Death Differ. 2011 Jan;18 (1):5-15.
KP. Lai, WF. Leong, JF. Chau, D. Jia, L. Zeng, H. Liu, L. He, A. Hao, H. Zhang, D. Meek, C. Velagapudi, SL. Habib, B. Li "S6K1 is a multifaceted regulator of Mdm2 that connects nutrient status and DNA damage response". EMBO J. 2010 Sep 1;29(17):2994-3006.
YL. Li, GZ. Wu, L. Zeng, GS. Dawe, L. Sun, G. Loers, T. Tilling, SS. Cui, M. Schachner, ZC. Xiao. "Cell surface sialylation and fucosylation are regulated by the cell recognition molecule L1 via PLCgamma and cooperate to modulate embryonic stem cell survival and proliferation". FEBS Lett. 2009 Feb 18;583(4):703-10.
QH. Ma, T. Futagawa, WL. Yang, XD. Jiang, L. Zeng, Y. Takeda, RX. Xu, D. Bagnard, M. Schachner, K. Watanabe, G. S. Dawe and Z. C. Xiao. "A TAG-1/APP signalling pathway through Fe65 negatively modulates neurogenesis". Nat. Cell Biol. 2008, 10 (3), 283-294.
L. Zeng, G.Z. Wu, K. J. Goh, Y. M. Lee, C. C. Ng, B. Y. Ang, J.H. Wang, D. Y. Jia, Ai. J. Hao, Q. Yu and B. J. Li "Saturated fatty acids modulate cell response to DNA damage: implication for their role in tumorigenesis". PLoS ONE, 2008. 3(6), e2329, 1-9.
YL. Li, GZ. Wu, GS. Dawe , L. Zeng, SS. Cui, G. Loers, T. Tilling, L. Sun, M. Schachner, ZC. Xiao. "Cell surface sialylation and fucosylation are regulated by L1 via phospholipase Cgamma and cooperate to modulate neurite outgrowth, cell survival and migration". PLoS ONE. 2008;3(12):e3841.
L. Zeng, Y. Y. Hu, and B. J. Li "Identification of TopBP1 as a c-Abl interacting protein and a repressor for c-Abl expression". J. Biol. Chem. 2005, 280 (32), 29374-29380.
Y. Y. Hu, X. Y. Wang, L. Zeng, D. Y. Cai, K. Sabapathy, S. P. Goff, E. J. Firpo and B. J. Li "ERK phosphorylates p66shc on Ser36 and subsequently regulates p27kip1 expression via the Akt-FOXO3a pathway: implication of p27kip1 in cell response to oxidative". Mol. Biol. Cell. 2005. 16 (8), 3705-3718.
D.Y. Nie, Z.H. Zhou, B.T. Ang, F.H. Teng, G. Xu, T. Xiang, C.Y. Wang, L. Zeng, Y. Takeda, T.L. Xu, Y.K. Ng, C. Faivre-Sarrailh, B. Popko, E.A. Ling, M. Schachner, K. Watanabe, C.J. Pallen, B.L. Tang and Z.C. Xiao. "Nogo-A at CNS paranodes is a ligand of Caspr: a possible role in regulating K+ channel localization". EMBO J. 2003. 22 (21), 5666-5678.
L. Zeng, X. N. Si, W. P. Yu, H. T. Le, K. P. Ng, M.H.Teng, K. Ryan, Z.M. Wang, S. Ponniah and C. J. Pallen “PTPα Regulates Integrin-Stimulated FAK Autophosphorylation and Cytoskeletal Rearrangement in Cell Spreading and Migration”. J Cell Biol. 2003. 160 (1), 137-46.
L. Zeng, L. D'Alessandri, M. B. Kalousek, L. Vaughan and C. J. Pallen “Protein Tyrosine Phosphatase α (PTPα) and Contactin Form a Novel Neuronal Receptor Complex Linked to the Interacellular Tyrosine Kinase fyn”. J Cell Biol. 1999. 147 (4), 707-713.
TEAM MEMBERS
Dr. ZHANG Wei, Ph.D
Dr. Zoë BICHLER, Ph.D (With A/Prof Tan)
Mr. HE Bing (Research Fellow)
Ms. Irene SOON (Lab Manager)
Mr. LIM HanChi (Snr Research Assistant)
Ms. Selvaratnam THEVAPRIYA (Snr Research Assistant)
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