Proteoglycans as Modulators of Cell/Matrix Interactions
Professor Shum, Daisy Kwok Yan (岑國欣)
Professor, Department of Biochemistry
BSc, MPhil, PhD (Hong Kong)
- Email: firstname.lastname@example.org
- Tel: (852) 2819-9171; 2819 9274 (lab)
- Office: L3-64, Laboratory Block, 21 Sassoon Road, Hong Kong
Postgraduate Research Projects Available:
- Growing new nerves in glycosaminoglycan-modified environments.
- Lung inflammation - control of matrix turnover.
The proteoglycans and their associated glycosaminoglycans are positioned in the extracellular matrix and the cell surface to maintain tissue architecture and foster tissue growth and repair. The corollary suggests that their altered expression in these positions or deranged metabolism leads to matrix deterioration. It follows that they are candidates for intervention in attempts to regulate tissue regrowth and repair.
Neuronal growth and repair: The roles of glycosaminoglycans in cell adhesion and neurite outgrowth are studied by the use of neuron/glial cell co-cultures in vitro and nerve bridges in vivo. Results will be applied in engineering nerve grafts and glial cell transplants to achieve functional repair in the adult CNS.
Chronic inflammatory diseases of the respiratory tract: The protective functions of soluble and matrix-bound forms of proteoglycans in proteolytic degradation of the bronchial matrix are investigated with the use of isolated inflammatory cells activated either by bronchial secretions or specific cytokines. We aim to apply the knowledge to the design of a therapeutic strategy that achieves optimal proteolytic activity for tissue repair but avoids excessive tissue destruction.
Renal stone formation: The roles of urinary glycosaminoglycans in modulating crystallization of urinary calcium oxalate are studied with a simple and rapid crystallization assay method with potential for wider application in screening for risk of stone formation. The control of urinary oxalate output through renal proteoglycan regulation of transepithelial oxalate transport is also studied in renal proximal tubular epithelial cell cultures. The renal cell cultures will be used also to study how apical secretion and surface expression of proteoglycans can affect crystal adhesion and growth.
Cancer biology: We use different cell lines to study the mechanisms by which proteoglycans mediate processes of growth control. A current project involves the study of how mutations in EXT genes change the expression of heparan sulfates and as a result alter the transport of signaling molecules important to the differentiation of chondrocytes in growth plate.
Publications, Achievements, and Grants:
- Liu J., Chau C.H., Liu H.Y., Jang B.R., Li X.G., Chan Y.S., Shum D.K.Y. (2006) Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth. J Cell Sci 119:933-942.
- Zhang Y., Yeung M.N., Liu J., Chau C.H., Chan Y.S., Shum D.K.Y. (2006) Mapping heparanase expression in the spinal cord of adult rats. J Comp Neurol 494:345-357.
- Chau C.H., Shum D.K.Y., Xu X.M. (2004). Combinatorial strategies towards spinal cord repair enhancement of the Schwann cell bridge and modification of the graft-host interface. Preclinica 2:409-415.
- Chau, C.H., Shum, D.K.Y., Li, H., Pei, J., Lui, Y.Y., Wirthlin, L., Chan, Y.S., and Xu, X.M. (2003) Chondroitinase ABC enhances axonal regrowth through Schwann cell-seeded guidance channels after spinal cord injury. FASEB Journal (18:194-6. 10.1096/fj.03-0196fje. Epub Nov20, 2003)
- Chan, S.C.H., Shum, D.K.Y., and Ip, M.S.M. (2003) Sputum sol neutrophil elastase activity in bronchiectasis: differential modulation by syndecan-1. Am. J. Respir. Crit. Care Med. 168, 192-198.
- Shum, D.K.Y. and Ip, M.S.M. (2002) Degradation of lung matrix proteoglycans in bronchiectasis. In: HG Garg, PJ Roughley and CA Hales (Eds). Proteoglycans in Lung Diseases in "Lung Biology in Health and Disease" Series. New York, New York, Marcel Dekker.
- Yick L.W., Wu, W, So K.F., and Shum, D.K.Y. (2000) Chrondroitinase ABC promotes axonal regrowth of Clarke's neurons into peripheral nerve graft after hemisection of the spinal cord. NeuroReport 11, 1063-1067.
- Chung, K.Y., Shum, D.K.Y., and Chan, S.O. (2000) Expression of chondroitin sulfate proteoglycans in the chiasm of mouse embryos. J. Comp. Neurol. 417, 153-163.
- Chung, K.Y., Taylor, J.S.H., Shum, D.K.Y., and Chan, S.O. (2000) Axon routing at the chiasm after enzymatic removal of chondroitin sulfate in mouse embryos. Development 127, 2673-2683.
- Shum, D.K.Y., Chan, S.C.H., and Ip, M.S.M. (2000) Neutrophil-mediated degradation of lung proteoglycans: stimulation by TNF-alpha in sputum of patients with bronchiectasis. Am. J. Respir. Cell. Crit. Care. Med. 162, 1925-1931.
- Shum, D.K.Y., Gohel, M.D.I., and Tam, P.C. (1999) Hyaluronans: crystallization-promoting activity and HPLC analysis of urinary excretion. J. Am. Soc. Nephrol. 10, 397-403.
- Chau, C.H., Shum, D.K.Y., Chan, Y.S., and So, K.F. (1999) Heparan sulfates upregulate regeneration of transected sciatic nerves of adult guinea pigs. Eur. J. Neurosci. 11, 1914-26.
- Shum, D.K.Y., and Chau, C.H. (1996) Changes in glycosaminoglycans during the regeneration of post-crush sciatic nerves of adult guinea pigs. J. Neurosci. Res. 46, 465-476.
- Shum, D.K.Y., and Liong, E. (1995) Calcium oxalate crystallization properties of polyanions elaborated by cultured renal proximal tubular cells. Urol. Res. 23, 103-110.
- Ip, M., Shum, D.K.Y., Lauder, I., Lam, W.K. and So, S.Y. (1993) Effect of antibiotics on sputum inflammatory contents in acute exacerbations of bronchiectasis. Resp. Med. 87, 449-454.
- Shum, D.K.Y., and Gohel, M.D.I. (1993) The separate effects of urinary chondroitin sulphate and heparan sulphate on the crystallization of urinary calcium oxalate: differences between stone formers and normal controls. Clin. Sci. 84, 33-39.