Dr David Wilkinson BSc MRes PhD

Tenure Track Fellow Musculoskeletal Biology II

    About

    Personal Statement

    I have a background in proteinase biology and investigating how the extracellular matrix is remodelled in both health and disease. In particular I have an interest in the interaction of the two major families of extracellular proteinase - the serine and metalloproteinases. Proteinases do not function in isolation (almost always produced as pro-enzymes) and are involved in a series of proteolytic cascades. In osteoarthritis (OA) the ultimate effector proteinase responsible for cartilage collagen destruction is often considered to be matrix metalloproteinase-13 (MMP-13). However, the events leading to its activation are far from understood, and represent novel avenues for therapy. My work seeks to understand which serine proteinases are important in effecting cartilage catabolism in OA (Wilkinson et al., 2017a, 2017b, 2018). Indeed, recent work has sought to understand the role of serine proteinase inhibitors (serpins) in protecting cartilage from unwanted proteolytic activity, and use their unique specificities to identify the target serine proteinase(s) which are important in disease. I am also interested in the role of proteinase-activated receptors (PARs) in promoting cartilage destruction. PARs are a unique form of membrane-bound receptor which are activated by a tethered ligand, generated by proteolytic cleavage (usually a serine proteinase) - the importance of which further highlights the integrated regulatory networks of serine and metalloproteinases (Falconer et al., 2019). I have also worked on projects investigating how metalloproteinases are regulated by cellular signalling events and the impact that this has on OA and cartilage destruction (Litherland et al, 2014; Radwan et al., 2014; Baker et al., 2018).

    After achieving a BSc in Molecular Biology and Biochemistry from Durham University, I joined Newcastle University in 2009 to undertake a PhD as part of the Oliver Bird Rheumatism Programme (Nuffield Foundation) in the Musculoskeletal Research Group (Institute of Cellular Medicine). Supervised by Professor Drew Rowan, my PhD focused on the role of type II transmembrane-anchored serine proteinases and their interactions with metalloproteinases to effect cartilage destruction (completed in 2014). I gained subsequent post-doctoral experience at Newcastle, moving to the Institute of Genetic Medicine in January 2017, before undertaking a Tenure Track Fellowship at University of Liverpool in July 2019.