Bone, Cartilage, Joint Development and Diseases

• HKU-SIRI
• Honorary research associate, Department of Orthopedic Surgery, HKU-Shenzhen Hospital

My research interest focus on the development and diseases in skeletal and connective tissues such as synovial joint, intervertebral discs, growth plate cartilage and bone. Development of novel therapeutic approaches through understanding the biology of skeletal development and pathogenic mechanism of diseases is also another research focus. One example of my research is the identification of Lgr5+ multipotent joint progenitor cells during embryonic synovial joint development. As these cells can differentiate into almost all kind of cells in an adult joint and could be a true type of progenitor cell for treating joint diseases such as osteoarthritis and ligament rupture. On-going projects include understanding the molecular control of these cells through single-cell transcriptome approach and the potential repair capacities of these progenitors in ligament/tendon and cartilage. Another ongoing project collaborating with Prof. Julian Tanner in our School, is using Oligonucleotide aptamer (also known as “chemical antibodies”) to enhance bone forming cells (osteoblasts) activities and differentiation to enhance bone mass and quality in low bone mass disorders such as osteoporosis and genetic disease Osteogenesis Imperfecta (Brittle bone disease).

1. Adrian OW Leung, Andrew CH Poon, Xue Wang, Chen Feng, Peikai Chen, ZF Zheng, Michael KT To, Wilson CW Chan (corresponding author), Martin Cheung & Danny Chan (2024) Suppression of apoptosis impairs phalangeal joint formation in the pathogenesis of brachydactyly type A1. Nature Communications volume 15, Article number: 2229
2. Feng C, Chan WCW Lam Y (co-first authors), Wang X, Chen PK, Niu B, Ng VCW, Yeo JC, Stricker S, Cheah KSE, Koch Manule, Mundlos S, Ng HH, Chan D. (2019) Lgr5 and Col22a1 mark progenitor cells in the lineage toward juvenile articular chondrocytes. Stem Cell Reports
3. Vivian Tam, Peikai Chen, Anita Yee, Nestor Solis, Theo Klein, Mateusz Kudelko, Wilson CW Chan, Christopher Overall, Lisbet Haglund, Pak C Sham, Kathryn S E Cheah, Danny Chan (2020) DIPPER, a spatiotemporal proteomics atlas of human intervertebral discs for exploring ageing and degeneration dynamics. 2020;9:e64940 DOI: 10.7554/eLife
4. Wang C, Tan ZJ, Niu B, Tsang KY, Tai A, Chan WCW, Lo RLK, Leung KKH, Dung NWF, Itoh N, Zhang MQ, Chan D, Cheah KSE. (2018) Inhibiting the integrated stress response pathway prevents aberrant chondrocyte differentiation thereby alleviating chondrodysplasia. eLife 2018;7:e37673
5. Zhang Y, Xiong C, Kudelko M, Li Y, Wang C, Wong YL, Tam V, Rai MF, Cheverud J, Lawson HA, Sandell L, Chan WCW, Cheah KSE, Sham PC, Chan D. (2018) Early onset of disc degeneration in SM/J mice is associated with changes in ion transport systems and fibrotic events. Matrix Biology Apr 9. pii: S0945- 053X(18)30076-3
6. Chan WCW, Tsang KY (co-first authors), Cheng YW, Ng VCW, Chik H, Tan ZJ, Boot-Handford R, Bodyde A, Cheung KMC, Cheah KSE, Chan D. (2017) Activating the unfolded protein response in osteocytes causes hyperostosis consistent with craniodiaphyseal dysplasia. Hum Mol Genet.
7. Tam V, Chan WCW (co-first authors), Leung VYL, Cheah KSE, Cheung KMC, Sakai D, McCann MR, Bedore J, Seguin CA, Chan D. (2017) Histological and reference system for the analysis of mouse intervertebral disc. J Orthop Res.
8. Shah A.M., Kwon S.Y.J., Chan WCW., Chan D. (2017) Intervertebral Disc Degeneration. In: Grä ssel S., Aszó di A. (eds) Cartilage pp229-261. Springer, Cham
9. Yee A, Lam MP, Tam V, Chan WCW, Chu IK, Cheah KSE, Cheung KMC, Chan D. (2016) Fibrotic-like changes in degenerate human intervertebral discs revealed by quantitative proteomic analysis. Osteoarthritis Cartilage. 24(3):503-13.
10. Wang X., Chan WCW, Chan D. (2016) Joint Development. In: Grä ssel S., Aszó di A. (eds) Cartilage pp169-189. Springer, Cham
11. Chan WCW, Au TY, Tam V, Cheah KS, Chan D (2014) Coming together is a beginning: the making of an intervertebral disc. Birth Defects Res C Embryo Today 102: 83-100.
12. Chan WCW, Sze KL, Samartzis D, Leung VY, Chan D (2011) Structure and biology of the intervertebral disk in health and disease. Orthop Clin North Am 42: 447-464, vii.
13. Klopocki, E., Lohan, S., Brancati, F., Koll, R., Brehm, A., Seemann, P., Dathe, K., Stricker, S., Hecht, J., Bosse, K., Betz, R. C., Garaci, F. G., Dallapiccola, B., Jain, M., Muenke, M., Ng, VC., Chan WCW., Chan, D., Mundlos, S. (2011) Copy-number variations involving the IHH locus are associated with syndactyly and craniosynostosis. Am J Hum Genet 88: 70-75.

As PI: 2019–2021 | Health and Medical Research Fund (HMRF) “Oligonucleotide Aptamers For The Treatment Of Low Bone Mass Disorders”

2018 | Best Presentation Award, Matrix Biology Europe
2017 | HKU LKS Faculty of Medicine Knowledge Exchange Award
2015 | Chairman of Gordon Research Seminar “Cartilage and Pathology”, Galveston, USA
2013 | Best Oral Presentation, 9th Pan Pacific Connective Tissue Societies Symposium

1. Preventive and Therapeutic Approach for Aberrant Cell Differentiation and ISR-Associated Diseases (16/335,395)
2. Multipotent Joint Progenitor Cells, Compositions and Methods Thereof (62/892,067)