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Dr CHEUNG, Martin Chi Hang 張知恆

Dr CHEUNG, Martin Chi Hang 張知恆

  • BSc (CUHK); PhD (U of Nottingham)
  • Associate Professor
L1-50, Laboratory Block, 21 Sassoon Road, Hong Kong
+852 3917 6867
+852 2817 0857
  • Genetic control of neural crest formation, delamination and migration
  • Live cell imaging of neural crest migratory behavior
  • Molecular mechanisms of melanoma metastasis and drug resistance
  • Modelling neurological diseases by cellular reprogramming
  • Research Assistant Professor, Department of Biochemistry, The University of Hong Kong, Hong Kong
  • Postdoctoral Fellow, Division of Developmental Neurobiology, The National Institute for Medical Research, London, United Kingdom
  • Ph.D., Division of Genetics, The University of Nottingham, United Kingdom
  • B.Sc. Hons (1st), Department of Biochemistry, The Chinese University of Hong Kong, Hong Kong

My research interest has been using neural crest as a platform to study the molecular regulation of cell migration and how its dysregulation leads to diseases such as cancer invasion with the long-term goal in applying knowledge gained to develop therapeutic strategies. 

Neural crest migration

The neural crest is formed as epithelial population of multipotent progenitors at the neural plate border during neural tube formation. These cells implement a transcriptional program in response to inductive signals such as BMPs and Wnts to initiate an epithelial to mesenchymal transition (EMT) characterized by the loss of cell-cell adhesion molecule, alteration of cytoskeletal structure and formation of focal adhesion complex to provide traction at the cell leading edge that endows cells with the capacity to delaminate and migrate to the periphery to form cranial facial structures, melanocytes and the peripheral nervous system. Our previous studies demonstrated a crucial role of Sox9, member of SoxE transcription factor family, in specifying neural crest identity and also inducing delamination from the dorsal trunk neural tube. Recently, we further showed that phosphorylation of Sox9 is required to regulate the onset of neural crest delamination and subjected to the regulation of BMP and canonical Wnt signaling. Currently, we are using chick embryo as a model system to functionally characterize the role of several novel regulators in neural crest development and how they mediate Sox9 function for controlling neural crest delamination and migration. Our approaches include gain- and loss-of-function analysis, gene expression profiling, neural tube explants, biochemical assays and live cell imaging.

Live cell imaging of RHOA biosensor showing a migrating neural crest cell with high RHOA activity in the cytoplasm of the cell rear relative to fluctuating RHOA activity in membrane protrusions at the leading front.

Melanoma

Another part of our research is based on the fact that neural crest EMT event is also recapitulated in cancer cells in which dysregulation of developmental genes confer their growth and invasive behavior. Consistently, our pilot studies revealed the role of Sox9 and Sox10 in contributing to the development and progression of neural crest-derived tumor, melanoma and similar regulators identified from above are also expressed in metastatic melanoma. At present, we are investigating whether these factors also function downstream of Sox9 and/or Sox10 in contributing to melanoma development. We have established collaboration with scientists from Spain, Scotland, China and HKU to investigate whether similar gene regulatory network in neural crest development also governs melanoma growth and metastasis.

Martin Cheung's lab photo-2019

Lab photo

For further enquiries, please email me: mcheung9@hku.hk

  1. Yang XT, Hu F, Liu JA, Yu Shan, Cheung MPL, Liu XL, Ng IOL, Guan XY, Wong KKW, Sharma R, Lung HL, Jiao YF, Lee LT and Cheung M*. Nuclear DLC1 exerts oncogenic function through association with FOXK1 for cooperative activation of MMP9 expression in melanoma. (2020) Oncogene https://www.nature.com/articles/s41388-020-1274-8.
    Behind the paper: https://cancercommunity.nature.com/channels/465-behind-the-paper/posts/64108-dlc1-is-oncogenic-in-melanoma
  2. Liu JA, Tai A, Hong JL, Cheung MPL, Sham MH, Cheah KSE, Cheung CW and Cheung M*. Fbxo9 functions downstream of Sox10 to determine neuron-glial fate choice in the dorsal root ganglia through Neurog2 destabilization. (2020) Proc Natl Acad Sci USA 117(8): 4199-421, https://www.pnas.org/content/early/2020/02/05/1916164117.
    Press release: HKUMed discovers new molecular mechanism in determining sensory neuron which paves the way for new therapeutic opportunities
  3. Cheung M, Tai A, Lu J and Cheah KSE. Acquisition of multipotent and migratory neural crest cells in vertebrate evolution. (2019) Current Opinion in Genetics & Development 57: 84-90, https://doi.org/10.1016/j.gde.2019.07.018.
  4. Yang XT, Liang R, Liu CX, Liu JA, Cheung MPL, Liu XL, Man OY, Guan XY, Lung HL and Cheung M*. Sox9 is a dose-dependent metastatic fate determinant in melanoma. (2019) Journal of Experimental and Clinical Cancer Research 38: 17, https://doi.org/10.1186/s13046-018-0998-6
  5. Wang YX, Liu JA, Leung KK, Sham MH, Chan D, Cheah KSE and Cheung M*. Reprogramming of mouse calvarial osteoblasts into induced pluripotent stem cells. (2018) Stem Cells International Article ID 5280793, https://doi.org/10.1155/2018/5280793.
  6. Liu JA, Rao YX, Cheung MPL, Hui MN, Wu M-H, Chan LK, Ng IOL, Niu B, Cheah KSE, Sharma R, Hodgson L and Cheung M*. Asymmetric localisation of DLC1 defines avian trunk neural crest polarity for directional delamination and migration. (2017) Nature Commun 8(1): 1185. doi: 10.1038/s41467-017-01107-0.

    (Press release in the Faculty homepage: https://www.med.hku.hk/news/press/2017/11)

  7. Wang YX, Wu MH, Cheung MPL, Sham MH, Akiyama H, Chan D, Cheah KSE and Cheung M*. Reprogramming of dermal fibroblasts into osteo-chondrogenic cells with elevated osteogenic potency by defined transcription factors. (2017) Stem Cell Reports 8(6): 1587-1599. 
  8. Liu JA and Cheung M*. Neural crest stem cells and their therapeutic applications. (2016) Dev Biol 419(2): 199-216. (Highlighted article in the journal homepage) 
    https://www.journals.elsevier.com/developmental-biology/highlighted-articles/db-ecr-mcheung
  9. Carrasco-Garcia E, Lopez L, Aldaz P, Arevalo S, Aldaregia J, Egana L, Bujanda L, Cheung M, Sampron N, Garcia I and Matheu A. SOX9-regulated cell plasticity in colorectal metastasis is attenuated by rapamycin. (2016) Sci Rep 6:32350.
  10. Kam MKM, Cheung M, Zhu JJ, Cheng WWC, Sat EWY, Tam PKH and Lui VCH. Perturbation of Hoxb5 signaling in vagal and trunk neural crest cells causes apoptosis and neurocristopathies in mice. (2014) Cell Death & Differentiation 21: 278-289.
  11. Liu JA, Wu MH, Yan CH, Chau BK, So H, Ng A, Chan A, Cheah KS, Briscoe J and Cheung M*. Phosphorylation of Sox9 is required for neural crest delamination and is required downstream of BMP and canonical Wnt singlaing. (2013) Proc Natl Acad Sci USA 110 (8): 2882-2887. (*Corresponding author)
  • HMRF (PI: 2020)
  • RGC General Research Fund (PI: 2010, 2015, 2016, 2017, 2019, 2020)
  • Hong Kong Scotland Collaborative Research Scholarship (PI: 2014)
  • RGC Early Career Scheme (PI: 2014)
  • Theme-based Research Scheme (Co-I: 2014-2019)
  • Seed Funding for Basic Research (PI: 2008, 2012, 2014-2020)

  • Faculty Outstanding Research Output Award 2018 (in the capacity of corresponding author), The University of Hong Kong
  • Research Output Prize 2010 (in the capacity of co-author), The University of Hong Kong
  • Ms May Cheung (Senior Technician)
  • Ms Lynn Hui (Research Assistant)
  • Ms Ng Jia Ying (Research Assistant)
  • Ms Hu Feng (PhD student, 2018 - )
  • Ms Shi Tianyuan (PhD student, 2018 - )
  • Ms Zheng Zhengfan (PhD student, 2018 - )
  • Mr. Umar Patel (HKPF awardee, 2020 - )
  • Ms Xu Zihan (UPF awardee, PhD student, 2020 - )
  • Mr. Dei Men Szeto (BSc Yr4: Final Year Project student, 2020)

Regular Student Consultation Hour: By appointment

  • Every Wednesday 11:00 am - 12:00 pm

Last update: 2020-10-19