Inflammation - Biochemical Pharmacology

As the name implies, the department of Biochemical Pharmacology seeks to understand the action of drugs at the biochemical level. Our main interest is in inflammation and anti-inflammatory drugs and in particular the mechanism of action of the anti-inflammatory glucocorticoids, probably the most powerful anti-inflammatory drugs in our armamentarium.

The glucocorticoids act on cells in several ways, causing changes in the rates of synthesis of key proteins as well as changing other fundamental cellular processes. We have been particularly interested in the activity of one protein called lipocortin (annexin) 1. Glucocorticoids cause changes in the synthesis and sub-cellular distribution of this protein and in doing so enable it to suppress signal transduction systems within cells and to exert anti-inflammatory, anti-proliferative and other effects.

The human recombinant protein has potent anti-inflammatory actions in its own right and, more importantly, these may be mimicked by short peptide sequences taken from the N-terminus of the protein.

Our current work is devoted to elucidating which actions of glucocorticosteroids are mediated through lipocortin 1, how this protein produces its striking biological actions and how we can build upon this knowledge to develop superior steroid-like anti-inflammatory drugs, but without the burden of side effects seen with these hormones.

Our work is supported largely by grants obtained from medical charities such as the Wellcome Trust, the Arthritis and Rheumatism Campaign and the British Heart Foundation.