Sashko Damjanovski, PhD
Developmental Biology - Extracellular Matrix Remodelling
Extracellular matrix remodelling in Developing Xenopus laevis
Healthy tissue function requires proper cell adhesion, and this adhesion is in part provided by proteins collectively known as the extracellular matrix (ECM). The ECM can be cut and remodelled by proteins called matrix metalloproteinases (MMPs). The function of MMPs is in turn regulated by inhibitors named RECK and TIMPs. Many cell types lose their normal functions when cell-ECM interactions are broken, in a process similar to the transformation of healthy cells into uncontrolled cancer cells. We use the frog, Xenopus laevis, as well as a number of cell lines as model systems to examine how specific ECM remodelling events control cell migration, invasion and ultimately cell fate. Several embryological and microinjection, as well as in vitro and in vivo cell culture techniques are used to investigate expression patterns, cell signalling events, and cytoskeletal rearrangements and how they are related to ECM remodelling events, and diverse processes such as cell proliferation, migration and death.
Currently we are focusing on a membrane bound MMP named MT1-MMP. MT1-MMP appears to be a key lynch-pin in several processes as it is believed to not only regulate ECM remodelling, but also to activate other MMPs, transduce signalling cascades, as well as impact cellular viability. Understanding this regulation would be crucial in our understanding of the roles that these molecules play in development and disease.
Bio2882b - Cell Biology Bio3338a - Developmental Biology
Articles in Peer-Reviewed Journals:
- Cepeda MA, Evered CL, Pelling JH, Damjanovski S. 2017. Inhibition of MT1-MMP proteolytic function and ERK1/2 signalling influences cell migration and invasion through changes in MMP-2 and MMP-9 levels. Journal of Cell Communication and Signalling. Jan 9. doi: 10.1007/s12079-016-0373-3.
- Cepeda MA, Pelling JH, Evered CL, Leong HS, Damjanovski S. 2017. The cytoplasmic domain of MT1-MMP is dispensable for migration augmentation but necessary to mediate viability of MCF-7 breast cancer cells. Exp Cell Res. pii: S0014-4827(16)30391-3. Doi: 10.1016/j.yexcr.2016.11.019.
- Cepeda, M., Pelling, J., Evered, C. Williams, K., Freedman, Z., Stan I., Willson, J., Leong, H., Damjanovski, S. 2016. Low expression of MT1-MMP is optimal to promote tumourigenesis of breast cancer cells and is not associated with widespread ECM degradation. BMC Molecular Cancer 15:65 DOI: 10.1186/s12943-016-0547-x
- Willson, J.A., Nieuwesteeg, M.A., Cepeda, M., Damjanovski, S. 2015. Analysis of Xenopus laevis RECK and its relationship to other vertebrate RECK sequences. Journal of Scientific Research and Reports. 6(7): 504-513, 2015. DOI : 10.9734/JSRR/2015/17044
- Nieuwesteeg, M.A., Willson, J.A., Cepeda, M., Damjanovski, S. 2014. Analysis of the effects of Tissue Inhibitor of Metalloproteinases-1, -2 and -3 N- and C-terminal domains on signaling markers during X. laevis development. All Res. J. Biol. 5(4):30-36. ISSN:2172-4784.
- Nieuwesteeg, M.A, Willson, J.A, Cepeda, M., Fox, M.A. Damjanovski, S. 2014. Functional characterization of tissue inhibitor of metalloproteinase-1 (TIMP-1) N- and C-terminal domains during Xenopus laevis development. Scientific World Journal 30;2014:467907. doi: 10.1155/2014/467907.
- Fox, M.A., Nieuwesteeg, M.A., Willson J.A. Cepeda, M., and Damjanovski, S. 2013. Knockdown of Pex11β reveals its pivotal role in regulating peroxisomal genes, numbers, and ROS levels in Xenopus laevis A6 cells. In vitro Cellular and Molecular Biology - Animal. Nov. 14. DOI: 10.1007/s11626-013-9710-5
- Nieuwesteeg, M. Walsh, L.A., Fox, M.A. and Damjanovski, S. 2012. Domain specific overexpression of TIMP-2 and TIMP-3 reveals MMP-independent functions of TIMPs during X laevis development. Biochem Cell Biol. Aug;90(4):585-95.
- Walsh, L.A., Cepeda, M.A. and Damjanovski, S. 2012. Analysis of MMP-dependent and independent functions of tissue inhibitor of metalloproteinase-2 on the invasiveness of breast cancer cells. J. Cell Commun. Signal. Jun;6(2):87-95.
- Shafer M.E.R., Willson J.A., Damjanovski, S. 2011. Expression analysis of the peroxiredoxin gene family during early development in Xenopus laevis. Gene Expression Patterns. Gene Expr Patterns. Dec;11(8):511-6.
- Walsh, L.A. and Damjanovski, S. 2011. IGF-1 increases invasive potential of MCF 7 breast cancer cells and induces activation of latent TGF-beta1 resulting in epithelial to mesenchymal transition. Cell Commun. Signal. May 2;9(1):10.
- Fox, M.A., Walsh, L.A., Nieuwesteeg, M. and Damjanovski, S. 2011. PEX11β induces peroxisomal gene expression and alters peroxisome number during early Xenopus laevis development. BMC Developmental Biology 11:24.
Articles in non-Peer-Reviewed Journals – Reviews
- Willson, J.A. and Damjanovski, S. 2014. Vertebrate RECK in development and disease. Research Trends: Trends in Cell and Molecular Biology. 9:95-105. ISSN: 0972-8449.
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