John Heath - Overview

We are interested in the specificity and dynamics of the interaction between polypeptide growth factors and signalling receptors. This dictates the biological activity of growth factors in vivo and provides the basis for therapeutic intervention in growth factor signalling pathways in cancer.

We have, in collaboration with the Cancer Research UK Receptor Structure Group, determined the 3D structures of several cytokines of the 'gp130' family and a recognition domain of the shared receptor gp130. These findings have been used to identify, the key recognition sites in both ligands and receptors. This leads to new ways of intervening in cytokine signalling pathways for therapeutic benefit. We are now studying the structure and composition of higher order complexes between receptors, ligands and effectors

Specific mutations in ligands or receptors can lead to pathological outcomes – including tumour formation in man. We have been studying the consequences of disease-associated mutations in receptors to understand how mutations lead to altered signalling functions. In some cases this involves an increase in receptor signalling activity as a result of structural changes in the interaction between the ligand and receptor. We are now using a number of new genetic technologies to further explore the role of receptor signalling dynamics in disease processes.