ABSTRACT OF RESEARCH BEING UNDERTAKEN

In people with RDEB, a fault in the type VII collagen gene means that the layers of the skin do not adhere, resulting in blistering from minimal trauma. People with RDEB are at significantly increased risk of developing squamous cell carcinoma (SCC) but we do not know why. These tumours can be fatal so it is a very big problem for people with RDEB.

In this project, SCC cells from RDEB patients will be compared with SCC cells from non-RDEB patients and how they invade the collagen layers in the skin will be investigated. The level of metalloproteinases (enzymes that break down collagen and are necessary for invasion) will be compared.

To answer the main question, a novel technology, called “small inhibitory RNA molecules”, will be used to inhibit expression of type VII collagen in both primary keratinocytes and the SCC cells. The researchers will then examine invasion, metalloproteinase expression and expression of factors that may lead to loss of the normal growth control mechanisms in cells, for example overproduction of cytokines, very tiny molecules that increase cell growth and metalloproteinase production.

The results of the above experiments should increase our understanding of why patients with RDEB develop SCC and, in the future, lead to the development of new therapeutic targets for their prevention.