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The cytoskeleton forms a dynamic framework inside cells, supporting their shape and their movement. My lab focusses on the cytoskeleton of endothelial cells, the cell that line blood vessels. In healthy blood vessels, the endothelial cells control the passage of oxygen and nutrients from the blood to the tissue below, and return waste products in the opposite direction. Their cytoskeleton regulates this barrier function, and also controls the shape of the cells to allow blood to flow smoothly over the surface. Dysregulation of the cytoskeleton leads to disruption of the normal barrier and pathological flow.
When tissues become deprived of oxygen, as in heart disease or stroke, the body can activate endothelial cells in existing blood vessels, causing them to grow out towards the diseased area and form new blood vessels. This process is called angiogenesis. These new blood vessels improve perfusion of the damaged tissue and promote healing and recovery.
Angiogenesis is also switched on in cancer. Tumour cells produce growth factors that mimic the normal angiogenic signal and cause the body to initiate tumour angiogenesis, supplying the cancer cells with oxygen and nutrients. While the normal function of angiogenesis is to promote healing, this tumour angiogenesis promotes the growth and spread of cancer.
Central to all of these functions of endothelial cells is dynamic regulation of the endothelial cytoskeleton. This controls the normal shape of endothelial cell in resting blood vessels, but also underpins the shape changes and cell movement required for angiogenesis. The focus of my lab is the discovery of regulators of the endothelial cytoskeleton. We use a combination of proteomic and genetic strategies to identify novel cytoskeleton regulators and then use detailed assays of endothelial cell function and of angiogenesis to understand how they contribute to these processes. The goal of our work is to understand this complex biological process and through this to identify new targets for therapeutic control of endothelial function in ischemic disease and in cancer.
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- 1 Finished
28/11/16 → 27/11/18
The cancer angiogenesis co-culture assay: In vitro quantification of the angiogenic potential of tumoroidsTruelsen, S. L. B., Mousavi, N., Wei, H., Harvey, L., Stausholm, R., Spillum, E., Hagel, G., Qvortrup, K., Thastrup, O., Harling, H., Mellor, H. & Thastrup, J., 7 Jul 2021, In: PLoS ONE. 16, 7, p. e0253258 e0253258.
Research output: Contribution to journal › Article (Academic Journal) › peer-reviewOpen AccessFile43 Downloads (Pure)
A functional antagonism between RhoJ and Cdc42 regulates fibronectin remodelling during angiogenesisSundararaman, A. & Mellor, H. H., 28 Aug 2020, (E-pub ahead of print) In: Small GTPases. 6 p.
Research output: Contribution to journal › Article (Academic Journal) › peer-reviewOpen AccessFile27 Downloads (Pure)
Dimethyl-2-oxoglutarate improves redox balance and mitochondrial function in muscle pericytes of individuals with diabetes mellitusFaulkner, A. R. M., Tamiato, A., Cathery, W. R., Rampin, A., Caravaggi, C. M., Jover Garcia, E., Allen, S., Mellor, H. H., Hauton, D., Heather, L. C., Spinetti, G. & Madeddu, P. R., 30 Jul 2020, (E-pub ahead of print) In: Diabetologia.
Research output: Contribution to journal › Article (Academic Journal) › peer-reviewOpen AccessFile24 Downloads (Pure)