Division of Life Science
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Nancy Yuk-Yu IP, JP

PhD Harvard
The Morningside Professor of Life Science
Director of the State Key Laboratory of Molecular Neuroscience
Academician, The Chinese Academy of Sciences

Email: boip@ust.hk

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Nancy Yuk-Yu IP
Research Interests
Molecular basis of neuronal development and plasticity; neurodegenerative diseases and drug discovery.

Prof. Ip’s major research focus is on signal transduction in the nervous system. In particular, she is interested in understanding the molecular signals that control the precise wiring of neuronal circuit essential for proper brain function. Her current research projects are aimed at elucidating the molecular mechanisms that underlie neuronal survival, differentiation, axon guidance, synapse development and plasticity. Research efforts are also directed at identifying novel molecular targets that are critically involved in the pathophysiology of neurodegenerative diseases, and using traditional Chinese medicine as a source to identify drug leads for neurological disorders.

Representative Publications:

  1. Zhou X., Chen Y., Mok K.Y., Zhao Q., Chen K., Chen Y., Hardy J., Li Y., Fu A.K.Y., Guo Q., Ip NY and for the Alzheimer’s Disease Neuroimaging Initiative (2018) Identification of genetic risk factors in the Chinese population implicates a role of immune system in Alzheimer’s disease pathogenesis. Proc Natl Acad Sci U S A. 2018 Feb 5.
  2. Huang H., Lin X., Liang Z., Zhao T., Du S., Loy M.M.T., Lai K.O., Fu A.K.Y. and Ip NY (2017) Cdk5-dependent phosphorylation of liprinα1 mediates neuronal activity-dependent synapse development. Proc Natl Acad Sci U S A. 2017 Jul 31.
  3. Stimulation of the Hippocampal POMC/MC4R Circuit Alleviates Synaptic Plasticity Impairment in an Alzheimer's Disease Model. Shen Y, Tian M, Zheng Y, Gong F, Fu AK, Ip NY. Cell Rep. 2016 Nov 8;17(7):1819-1831. doi: 10.1016/j.celrep.2016.10.043.
  4. The pseudokinase CaMKv is required for the activity-dependent maintenance of dendritic spines. Liang Z, Zhan Y, Shen Y, Wong CC, Yates JR 3rd, Plattner F, Lai KO, Ip NY. Nat Commun. 2016 Oct 31;7:13282. doi: 10.1038/ncomms13282. PMID: 27796283 Free PMC Article
  5. IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline. Fu AK, Hung KW, Yuen MY, Zhou X, Mak DS, Chan IC, Cheung TH, Zhang B, Fu WY, Liew FY, Ip NY. Proc Natl Acad Sci USA 2016 May 10;113(19):E2705-13. doi: 10.1073/pnas.1604032113.
  6. S-nitrosylation-dependent proteasomal degradation restrains Cdk5 activity to regulate hippocampal synaptic strength. Zhang P, Fu WY, Fu AK, Ip NY. Nat Commun. 2015 Oct 27;6:8665. doi: 10.1038/ncomms9665.
  7. Anemoside A3 Enhances Cognition through the Regulation of Synaptic Function and Neuroprotection. Ip FC, Fu WY, Cheng EY, Tong EP, Lok KC, Liang Y, Ye WC, Ip NY. Neuropsychopharmacology. 2015 Jul;40(8):1877-87. doi: 10.1038/npp.2015.37.
  8. Fang, W.Q., Chen, W.W., Jiang, L., Liu, K., Yung, W.H., Fu, A.K., and Ip NY (2014). Overproduction of Upper-Layer Neurons in the Neocortex Leads to Autism-like Features in Mice. Cell Rep. 9(5):1635-43.
  9. Ye, T., Ip, J.P., Fu, A.K., and Ip NY (2014). Cdk5-mediated phosphorylation of RapGEF2 controls neuronal migration in the developing cerebral cortex. Nat Commun. 5:4826. doi: 10.1038/ncomms5826.
  10. Fu, A.K., Hung, K.W., Huang, H., Gu, S., Shen, Y., Cheng, E.Y., Ip, F.C., Huang, X., Fu, W.Y., and Ip NY (2014). Blockade of EphA4 signaling ameliorates hippocampal synaptic dysfunctions in mouse models of Alzheimer's disease. Proc Natl Acad Sci USA 111(27):9959-64.
  11. Fang, W.-Q., Chen, W.-W., Fu, A.K., and Ip NY (2013). Axin directs the amplification and differentiation of intermediate progenitors in the developing cerebral cortex. Neuron, 79(4):665-79.
  12. Shen, Y., Fu, W.Y., Cheng, E.Y.L., Fu, A.K.Y., and Ip NY (2013). Melanocortin-4 receptor regulates hippocampal synaptic plasticity through PKA-dependent mechanism. J. Neurosci., 33(2):464-472.
  13. Lai, K.O., Wong, A.S.L., Cheung, M.C., Xu, P., Liang, Z.Y., Lok, K.C., Xie, H., Palko, M.E., Yung, W.H., Tessarollo, L., Cheung, Z.H. and Ip NY (2012). TrkB phosphorylation by Cdk5 is required for activity-dependent structural plasticity and spatial memory. Nat. Neurosci.. 15:1506-1515.
  14. Shi, L., Fu, A.K.Y., and Ip NY (2012). Molecular mechanisms underlying the maturation and maintenance of the vertebrate neuromuscular junction. Trends in Neurosci., 35:441-53. Invited.
  15. Chen, Y., Fu, A.K.Y., and Ip NY. (2012). Eph receptors at synapses: Implications in neurodegenerative diseases. Cellular Signaling, 24:606-611. Invited.
  16. Ip, J.P., Shi, L., Chen, Y., Itoh, Y., Fu, W-Y, Betz, A., Yung, W-H, Gotoh, Y., Fu, A.K., and Ip NY (2012). α-chimaerin controls neuronal migration and functioning of the cerebral cortex through CRMP-2. Nat. Neurosci., 15:39-47.
  17. Fang, W-Q, Ip, J.P., Li, R., Ng, Y.P., Lin, S-C, Chen, Y., Fu, A.K., and Ip NY (2011). Cdk5-mediated phosphorylation of axin directs axon formation during cerebral cortex development. J. Neurosci., 31(38):13613-24.
  18. Fu, A.K., Hung, K.W., Fu, W.-Y., Shen, C., Chen, Y., Xia, J., Lai, K.O. and Ip NY (2011). APCCdh1 mediates EphA4-dependent downregulation of AMPA receptors in homeostatic plasticity. Nat. Neurosci., 14: 181-9.
  19. Wong, A.S., Lee, R.H., Cheung, A.Y., Yeung, P.K., Chung, S.K., Cheung, Z.H., and Ip NY (2011). Cdk5-mediated phosphorylation of endophilin B1 is required for induced autophagy in models of Parkinson’s disease. Nat. Cell Biol. 13:568-579.
  20. Ip NY(2011). Career development for women scientists in Asia. Neuron. 70:1029-1032.4.
  21. Cheung, Z.H. and Ip NY (2011). Cyclin-dependent kinase 5 – an emerging player in Parkinson’s disease pathophysiology. Parkinson’s Disease / Book six, P.141-156. Invited.
  22. Cheung, Z.H. and Ip NY (2012). Cdk5: a multifaceted kinase in neurodegenerative diseases. Trends Cell Biol., 846:1-7. Invited.
  23. Lai, K.O. and Ip NY (2012). Eph receptor. Encyclopedia of Signaling Molecules. Springer, P.560-567. Invited.
  24. Shi, L., Butt, B., Ip, F.C.F., Dai, Y., Jiang, L., Yung, W.H., Greenberg, M.E., Fu, A.K.Y., and Ip NY (2010). Ephexin1 is required for structural maturation and neurotransmission at the neuromuscular junction. Neuron 65: 204–216.
  25. Wan, J., Fu, A.K.Y., Ip, F.C.F., Ng, H.K., Hugon, J., Page, G., Wang, J.H., Lai, K.O., Wu, Z., an Ip NY (2010). Tyk2/STAT3 signaling mediates Ab-induced neuronal cell death: Implications in Alzheimer’s disease. J. Neurosci. 30(20): 6873-6881.
  26. Zhang, P., Yu, P-C, Tsang, A.H.K., Chen, Y, Fu, A.K., Fu, W.-Y., Chung, K.K., and Ip NY (2010). S-nitrosylation of cyclin-dependent kinase 5 (Cdk5) regulates its kinase activity and dendrite growth during neuronal development. J. Neurosci., 30(43):14366-14370.
  27. Lai, K.O. and Ip NY (2009). Synapse formation and plasticity: roles of ephrin/Eph receptor signaling. Current Opinion in Neurobiology 19: 1-9. Invited.
  28. Ip NY and Lu, B. (2009). Neurotrophic factors, in Neuroscience (3rd edition) (ed. J-S Han, M-M Poo and Y Rao), 26:474-489. Invited.
  29. Fu, A.K.Y. and Ip NY (2008). CDK5, in Targeted Proteins Database /1, [22945], 10.2970/tpdb.2009.264. Invited.
  30. Cheung, Z.H. and Ip NY (2008). Cdk5 in dendrite and synapse development: emerging role as a modulator of receptor tyrosine kinase signaling, in Cyclin Dependent Kinase 5 (Cdk5) (ed. N.Y Ip and L.-H. Tsai), Springer Science+Business Media, LLC, P51-68.
  31. Shi, L., Fu, W.-Y., Hung, K.-W., Porchetta, C., Hall, C., Fu, A.K.Y., and Ip NY (2007). α2-chimaerin interacts with EphA4 and regulates EphA4-dependent growth cone collapse. Proc. Natl. Acad. Sci. USA 104: 16347-16352.
  32. Cheung, Z.H., Chin, W.H., Chen, Y., Ng, Y.P., and Ip NY (2007). Cdk5 is involved in BDNF-stimulated dendritic growth in hippocampal neurons. PLoS Biol. 5(4): 865-877.
  33. Fu, W.Y., Chen, Y., Sahin, M., Zhao, X.S., Shi, L., Bikoff, J.B., Lai, K.O., Yung, W.H., Fu, A.K.Y., Greenberg, M.E., and Ip NY (2007). Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism. Nat. Neurosci. 10: 67-76.
  34. Cheung, Z.H., Fu, A.K.Y., and Ip NY (2006). Synaptic roles of Cdk5: implications in higher cognitive functions and neurodegenerative diseases. Neuron 50: 13-18. Invited review.
  35. Fu, A.K.Y., Ip, F.C.F., Fu, W.Y., Cheng, J., Wang, J., Yung, W.H., and Ip NY (2005). Aberrant motor axon projection, AChR clustering and neurotransmission in cyclin-dependent kinase 5 null mice. Proc. Natl. Acad. Sci. USA 102: 15224-15229.
  36. Luo, S., Chen, Y., Lai, K.O., Arevalo, J.C., Froehner, S., Adams, M.E., Chao, M., and Ip NY (2005). α-Syntrophin regulates ARMS localization at the neuromuscular junction and enhances EphA4 signaling in an ARMS-dependent manner. J. Cell Biol. 169: 813-824.
  37. Fu, A.K.Y., Fu, W.Y., Ng, A.K.Y., Chien, W.W.Y., Ng, Y.P., Wang, J., and Ip NY (2004). Cyclin-dependent kinase 5 phosphorylates signal transducer and activator of transcription 3 and regulates its transcriptional activity. Proc. Natl. Acad. Sci. USA 101: 6728-6733.
  38. Cheng, K., and Ip NY (2003). Cdk5: A new player at synapses. NeuroSignals 12: 180-190. Invited.
  39. Lai, K.O., and Ip NY (2003). Central synapse and neuromuscular junction: same players, different roles. Trends in Genetics 19: 395-402. Invited.
  40. Fu, A.K.Y., Fu, W.Y., Cheung, J., Tsim, K.W.K., Ip, F.C.F., Wang, J.H., and Ip NY (2001). Cdk5 is involved in neuregulin-induced acetylcholine receptor expression at the neuromuscular junction. Nature Neuroscience 4: 374-381.
  41. Ip NY and Shahi, G. (1998). A molecular biology network for Asia and the Pacific Rim. Science 280: 1708.
  42. Ip NY , and Yancopoulos, G.D. (1996). The neurotrophins and CNTF: Two families of collaborative neurotrophic factors. Ann. Rev. Neurosci. 19: 491-515. Invited.
  43. Ip NY , Boulton, T.G., Li, Y., Verdi, J.M., Birren, S.J., Anderson, D.J., and Yancopoulos, G.D. (1994). CNTF, FGF and NGF collaborate to drive the terminal differentiation of MAH cells into post-mitotic neurons. Neuron 13: 443-455.
  44. Lohof, A.M., Ip NY, and Poo, M.-m. (1993). Potentiation of developing neuromuscular synapses by the neurotrophins NT-3 and BDNF. Nature 363: 350-353.
  45. Davis, S., Aldrich, T., Stahl, N., Pan L., Taga, T., Kishimoto, K., Ip NY , and Yancopoulos, G.D. (1993). LIFR b and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor. Science 260: 1805-1808.
  46. Ip NY , Stitt, T.N., Tapley, P., Klein, R., Glass, D.J., Fandl, J., Greene L.A., Barbacid, M., and Yancopoulos, G.D. (1993). Similarities and differences in the way neurotrophins interact with the Trk receptors in neuronal and nonneuronal cells. Neuron 10: 137-149.
  47. Ip NY , McClain, J., Barrezueta, N., Aldrich, T.H., Pan, L., Li, Y., Wiegand, S.J., Friedman, B., Davis, S., and Yancopoulos, G.D. (1993). The a component of the CNTF receptor is required for signaling and defines potential CNTF targets in the adult and during development. Neuron 10: 89-102.
  48. Friedman, B., Scherer, S.S., Rudge, J.S., Helgren, M., Morrisey, D., McClain, J., Wang, D.-W., Wiegand, S.J., Furth, M.E., Lindsay, R.M. and Ip NY (1992). Regulation of ciliary neurotrophic factor expression in myelin-related Schwann cells in vivo. Neuron 9: 295-305.
  49. Ip NY , Nye, S.H., Boulton, T. G., Davis, S., Taga, T., Li, Y., Birren, S.J., Yasukawa, K., Kishimoto, T., Anderson, D.J., Stahl, N., and Yancopoulos, G.D. (1992). CNTF and LIF act on neuronal cells via shared signalling pathways that involve the IL-6 signal transducing receptor component gp130. Cell 69: 1121-1132.


Molecular Neuroscience Center Homepage: http://www.ust.hk/~mnc/


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