+44 (0) 1865 617586
Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK
Principal Investigator, Cellular Signalling
We are interested in understanding the molecular mechanisms of proteins involved in cellular signalling, especially those involved in signalling via post-translational modifications such as phosphorylation or ADP-ribosylation. Phosphorylation is catalysed by protein kinases; there are over 500 protein kinases in the human genome and most of them remain poorly characterized despite their importance regulating physiology. Our approach is to use high resolution structural information for the generation of selective inhibitors (chemical probes) which we use to gain understanding of the functions of these largely uncharacterized proteins. Our lab generated a large repository of efficient expression systems, recombinant proteins and crystal structures that now enables family wide structural comparison and screening. ADP-ribosylation is important in numerous cellular processes; as well as a well-established role in DNA damage detection and repair it is also important for host-virus interactions, epigenetic regulation and metabolism. We also have interests in lipid kinases and sphingolipid biosynthesis, which both have strong links to inflammation and cancer, and where mutations in the various proteins involved are associated with a variety of rare diseases.
Structure-kinetic relationship reveals the mechanism of selectivity of FAK inhibitors over PYK2.
Berger B-T. et al, (2021), Cell Chem Biol
Aminothiazolones as potent, selective and cell active inhibitors of the PIM kinase family.
Quevedo CE. et al, (2020), Bioorg Med Chem, 28
Mining Public Domain Data to Develop Selective DYRK1A Inhibitors.
Henderson SH. et al, (2020), ACS Med Chem Lett, 11, 1620 - 1626
Targeting the Water Network in Cyclin G-Associated Kinase (GAK) with 4-Anilino-quin(az)oline Inhibitors.
Asquith CRM. et al, (2020), ChemMedChem, 15, 1200 - 1215