Kwok-On LAI （黎國安）
Office: L4-40, Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong
Phone: (852) 3917 9521
Fax: (852)2855 9730
HKU Scholars Hub
Dr. Kwok-On Lai received his Bachelor degree of Biochemistry from the University of Hong Kong. He then pursued postgraduate studies at the Hong Kong University of Science and Technology (HKUST). With the award of the Croucher Foundation Fellowship in 2003, he performed postdoctoral research at UCLA in the United States. He was Research Assistant Professor at HKUST before joining the Department of Physiology in 2014. Using a combination of molecular, biochemical and cellular approaches, Dr. Lai aims to elucidate the signal transduction mechanisms that underlie the development and functioning of neuronal synapses in the brain. This would lead us to a better understanding of the cellular and molecular mechanisms underlying long-term memory, and the pathophysiology of various neurodevelopmental disorders in the brain.
The brain is remarkably flexible, an essential feature that enables adaptation to changes in the environment. This “plastic” nature of the brain is attributed to the ability of neurons to change their synaptic connectivity by experience. Synaptic plasticity involves structural modification of synapses, and depends on multiple cellular processes such as re-organization of cytoskeleton, local dendritic protein synthesis near synapses, and gene transcription in the nucleus.
Dendritic spines are specialized protrusions on dendrites where most excitatory synapses are present. Spines are highly dynamic, and their development and morphology are tightly regulated by activity. I am interested in understanding the signal transduction mechanisms by which neuronal activity sculpts dendritic spines. Using a combination of molecular, biochemical and cellular approaches, I have been focusing on how protein phosphorylation by kinases, such as the receptor tyrosine kinase TrkB and the serine/threonine kinase Cdk5, is involved in activity-dependent changes in spine morphogenesis. Protein phosphorylation is arguably the most-studied form of post-translational modification of proteins in signal transduction. However, emerging studies have uncovered many other ways by which proteins are post-translationally modified, although their functional significance in neuron remains elusive. One of my research focuses is to elucidate whether and how these post-translational modifications of synaptic proteins regulate synapse development and function.
Another area of research is to study the role of local protein synthesis in the regulation of dendritic spine development. It is well-established that there are subsets of mRNAs that are not only localized in the neuronal cell body but can also be transported to distal dendrites, where local protein synthesis is believed to regulate synaptic transmission efficacy of individual synapses. Numerous dendritically localized mRNAs have been recently identified in neurons, yet the functions of many of these mRNAs and their encoded proteins have not been characterized. The transcriptomic studies on the dendritic mRNAs should therefore represent important resources to identify novel proteins and signaling pathways that modulate dendritic spine morphogenesis. I aim to examine how these mRNAs are targeted to dendrites and the regulation of their synthesis by synaptic activity, and explore their function and underlying mechanisms in the regulation of spine morphogenesis and synaptic function.
Lai KO*, Liang ZY, Fei E, Huang H, Ip NY* (2015) Cdk5-dependent phosphorylation of p70 ribosomal S6 kinase (S6K) is required for dendritic spine morphogenesis. J. Biol. Chem. in press (*corresponding authors).
Lai KO, Ip NY (2013) Structural plasticity of dendritic spines: The underlying mechanisms and its dysregulation in brain disorders. Biochim. et Biophys. Acta.1832: 2257-2263.
Lai KO, Wong ASL, Cheung MC, Xu P, Liang Z, Lok KC, Xie H, Palko ME, Yung WH, Tessarollo L, Cheung ZH, Ip NY. (2012) Serine phosphorylation of TrkB by Cdk5 is required for activity-dependent structural plasticity and spatial memory. Nat. Neurosci. 15: 1506-1515.
Fu AK, Hung KW, Fu WY, Shen C, Chen Y, Xia J, Lai KO, Ip NY. (2011) APC(Cdh1) mediates EphA4-dependent downregulation of AMPA receptors in homeostatic plasticity. Nat. Neurosci. 14: 181-189.
Lai KO, Ip NY (2009) Synapse formation and plasticity: roles of ephrin/Eph receptor signaling. Curr. Opin. Neurobiol. 19: 275-283.
Lai KO, Zhao Y, Ch’ng TH, Martin KC (2008) Importin-mediated retrograde transport of CREB2/ATF4 from distal processes to the nucleus in neurons. Proc. Natl. Acad. Sci. U.S.A. 44: 17175-17180.