• Cellular, Molecular, and Developmental Neurobiology
  • Extracellular Matrix Remodeling in Synaptic Development
  • Cytoskeletal Dynamics in Motor Neuron Development and Disease
• Muscle Physiology and Pathophysiology
  • Neurotrophic Signaling in Muscle Physiology and Disease
  • Mitochondrial Dynamics and Function in Muscle Physiology and Disease

Dr. Lee Chi Wai joined the School of Biomedical Sciences at HKU as an Assistant Professor in September 2015.  He obtained his B.Sc. and Ph.D. from The Hong Kong University of Science & Technology in 2001 and 2005, respectively. With the support of The Croucher Fellowship, Dr. Lee received his postdoctoral training at Rutgers, then at Emory University in the United States.  Prior to joining HKU, Dr. Lee was an Assistant Professor and Principal Investigator of the Laboratory of Neuronal Development & Diseases in the Department of Physiology at National University of Singapore since 2013.  The research interest of his laboratory focuses on the signal transduction and cytoskeletal mechanisms underlying synapse development, disease, and regeneration.  His original research findings have been published in leading international journals including Nature Neuroscience, Current Biology, Journal of Neuroscience, PNAS, EMBO Journal, Molecular Biology of the Cell, and Developmental Biology.

Synapses are specialized cell membrane domains that facilitate neuronal communication in the intricate nervous system. These synaptic specializations develop in response to molecular interactions between pre- and postsynaptic cells. A major goal of current research in developmental neuroscience is to elucidate the mechanisms underlying how synapses are assembled. The nerve-muscle synapse, neuromuscular junction (NMJ), which controls all muscle movements, has been considered as the best model for the study of synaptogenesis due to its large size, simplicity and accessibility. When neurons and muscle cells are cultured together, functional NMJs are formed spontaneously. The structure and physiology of mature vertebrate NMJs are well understood.  Currently, our laboratory specifically focuses on the signal transduction and cytoskeletal mechanisms underlying synapse development, disease, and regeneration. Three major areas are being pursued in our lab:

1. Postsynaptic receptor trafficking in the pathogenesis of muscular dystrophy;

2. Cytoskeletal dynamics in neuronal growth cones during axonal outgrowth and pathfinding;

3. Axonal trafficking of mitochondria in synaptic formation, function, and elimination.

Using the simple and elegant Xenopus primary culture system, a variety of techniques, including live-cell time-lapse fluorescence microscopy, super-resolution microscopy, molecular biology, immunocytochemistry, and Western blotting will be applied to these experimental systems to gain understanding to the cellular and molecular mechanism of synaptic development. Our goal is to not only gain a mechanistic understanding of the molecular and cellular aspects of neuronal structure and function, but also provide insights into the cellular basis for neurological disorders.

• MMP-mediated ECM modulation and synapse development
• Proteolytic regulation of BDNF activity in neuromuscular junction formation
• Mechanoregulation of synapse development, function, and regeneration

(^*Co-first authors; ^#Corresponding author)

1. Yu J^*, Oentaryo MJ^* and Lee CW^# (2021) Local protein synthesis of neuronal MT1-MMP for agrin-induced presynaptic development. Development. May 15; 148(10): dev199000. doi: 10.1242/dev.199000. (5-Year Impact Factor: 6.19)
2. Chan ZC^*, Deng L^*, and Lee CW^# (2020) Grp94 regulates the recruitment of aneural AChR clusters for the assembly of postsynaptic specializations by modulating ADF/cofilin activity and turnover. eNeuro. Sep 8; 7(5): ENEURO.0025-20.2020. doi: 10.1523/ENEURO.0025-20.2020. (1-Year Impact Factor: 3.54)
3. Oentaryo MJ, Tse AC, and Lee CW^# (2020) Neuronal MT1-MMP mediates ECM clearance and Lrp4 cleavage for agrin deposition and signaling in presynaptic development. Journal of Cell Science. Aug 5; 133(15): jcs246710. doi: 10.1242/jcs.246710. (5-Year Impact Factor: 4.90)
   • Featured in Research Highlights of the issue - “MT1-MMP paves the way for agrin-induced presynaptic differentiation”.
4. Chan ZC, Kwan HR, Wong YS, Jiang Z, Zhou Z, Tam KW, Chan YS, Chan CB, and Lee CW^# (2020) Site-directed MT1-MMP trafficking and surface insertion regulate AChR clustering and remodeling at developing NMJs. eLife. Mar 24; 9: e54379. doi: 10.7554/eLife.54379. (5-Year Impact Factor: 8.18)
   • Featured in eLife Science Digests - “Clearing space to move”.
   • Recommended in Faculty Opinions.
5. Chan ZC^*, Oentaryo MJ^*, and Lee CW^# (2020) MMP-mediated modulation of ECM environment during axonal growth and NMJ development. Neuroscience Letters. Apr 17; 724: 134822. doi: 10.1016/j.neulet.2020.134822. (5-Year Impact Factor: 2.28) [Invited Review]
   • Published in the Special Issue - “The NMJ as a Model Synapse: New Perspectives on Formation, Synaptic Transmission and Maintenance”.
6. Yang X, Brobst D, Chan WS, Tse MC, Herlea-Pana O, Ahuja P, Bi X, Zaw AM, Kwong ZS, Jia W, Zhang Z, Zhang N, Chow SK, Cheung WH, Louie JC, Griffin TM, Nong W, Hui JH, Du G, Noh HL, Saengnipanthkul S, Chow BK, Kim J, Lee CW^#, and Chan CB^# (2019) Muscle-generated BDNF is a sexually dimorphic myokine that controls metabolic flexibility. Science Signaling. Aug 13; 12(594): eaau1468. doi: 10.1126/scisignal.aau1468. (5-Year Impact Factor: 6.94)
   • Featured in The Pulse, Circulation Vol 140, No. 24.
   • Featured in BioWorld (Clarivate Analytics) Vol 30, No. 157.
7. Yeo HL, Lim JY, Fukami Y, Yuki N, and Lee CW^# (2015) Using Xenopus tissue cultures for the study of myasthenia gravis pathogenesis. Developmental Biology. Dec 15; 408(2): 244-51. doi: 10.1016/j.ydbio.2015.02.017. (5-Year Impact Factor: 3.09)
   • Published in the Special Issue - “Modeling Human Development and Disease in Xenopus”.
8. Lee CW, Vitriol EA, Shim S, Wise AL, Velayutham RP, and Zheng JQ (2013) Dynamic localization of G-actin during membrane protrusion in neuronal motility. Current Biology. Jun 17; 23(12):1046-56. doi: 10.1016/j.cub.2013.04.057. (5-Year Impact Factor: 10.17)
9. Gu J^*, Lee CW^*, Fan Y^*, Komols D, Tang X, Sun C, Yu K, Hartzell HC, Chen G, Bamburg JR, and Zheng JQ (2010) ADF/cofilin-mediated actin dynamics regulate AMPA receptor trafficking during synaptic plasticity. Nature Neuroscience. Oct; 13(10):1208-15. doi: 10.1038/nn.2634. ( ^*Co-first authors) (5-Year Impact Factor: 21.50)
10. Lee CW, Han J, Bamburg JR, Han L, Lynn R, and Zheng JQ (2009) Regulation of acetylcholine receptor clustering by ADF/cofilin-directed vesicular trafficking. Nature Neuroscience. Jul; 2(7):848-56. doi: 10.1038/nn.2322. (5-Year Impact Factor: 21.50)
    • Recommended by 3 faculty members in F1000Prime.

• Principal Investigator
  • RGC (Hong Kong) – General Research Fund 2020–2022
  • RGC (Hong Kong) – General Research Fund 2019–2021
  • FHB (Hong Kong) – Health and Medical Research Fund 2017–2020
  • RGC (Hong Kong) – Early Career Scheme 2017–2020
  • MoE (Singapore) – AcRF Tier 1 Grant 2013–2015
  • Muscular Dystrophy Association (USA) – Development Grant 2011–2014

• Travel Grant, genesis: The Journal of Genetics and Development 2014
• MBL-JUSTL Summer Research Fellowship 2012
• Postdoctoral Merit Award, Emory University 2011
• Croucher Foundation Fellowship 2006–2008
• The George K Lee Foundation Postgraduate Scholarship 2005
• The Providence Foundation Undergraduate Scholarship 2000

• Review Editor, Frontiers in Synaptic Neuroscience 2014–Now

• TSE, Chung Kwan Anna (Technical Officer; 2016–Now)
• CHAN Chui Kuen, Zora (PhD Student; 2016–Now)
  • Tigris Education Fund (2017)
  • Travel Award, 37th Australasian Neuroscience Society Annual Meeting (2017)
  • Oral Presentation Award, Hong Kong Inter-University Postgraduate Symposium in Biomedical Sciences (2019)
• OENTARYO Marilyn Janice (PhD Student; 2016–Now)
  • Lee Shau Kee Postgraduate Fellowship (2016–2020)
• YU Jun (PhD Student; HKU-SUSTech Joint Programme; 2016–Now)
• KWAN Hiu Lam Rachel (PhD Student; 2019–Now)
  • HKU Foundation Postgraduate Fellowship (2019–2023)
  • HKU Postgraduate Fellowships in Integrative Medicine (2019–2021)