Dr Ewa Paleolog
Research focus: The vasculature and chronic inflammatory disease
Blood vessels play a central gatekeeper role in vivo, regulating inflammatory cell trafficking and the supply of oxygen and nutrients to tissues. Many diseases have been shown to be associated with changes in inflammatory molecules and/or altered blood vessel growth (termed ‘angiogenesis’). Rheumatoid arthritis (RA) is the archetypal chronic inflammatory disease. Despite the advent of biological therapies for RA, it is important to develop other approaches for the treatment of this debilitating disease. Interestingly, RA has been shown to be associated with an increase in the density of blood vessels in the synovium, which invades and subsequently destroys joint sand soft tissue, suggesting that angiogenesis may be an important therapeutic target in RA.
The research focus of my group is to understand the molecular changes which underlie angiogenesis in the context of chronic inflammatory diseases, especially RA, using a combination of cell culture approaches, molecular biology techniques and relevant disease models. Currently, we are studying the signalling pathways involved in the induction of angiogenic factor release, focusing in particular on vascular endothelial growth factor (VEGF). Specifically we are studying the effect of hypoxia, which is a potent signal to form new blood vessels, on cellular responses. We are also comparing the effectiveness of blocking angiogenic signals such as VEGF and epidermal growth factor in relevant disease models.
The long-term goals of our research are to understand the role of the vasculature and to develop alternative therapeutic approaches for RA. This research area has interesting translational potential, in that angiogenesis has been a putative target in cancer since it was first linked to tumour growth and metastases in the 1970s. The most successful anti-angiogenic approach is anti-VEGF antibody (bevacizumab), approved in for patients with colorectal cancer. It is likely that, as in the oncological setting, angiogenesis is fundamental in RA and represents a potentially attractive target for therapy.
