Dr Angus Wann
Kennedy Institute of Rheumatology
University of Oxford
Primary cilia, Inflammatory signalling, Osteoarthritis, endocytosis
The research group here is focused on a novel roles for the primary cilium in transducing signalling within contexts of pathology. This includes the response of cells to ‘inflammatory’ stimuli such as cytokines and pathophysiological mechanics.
Previous work illuminated a reciprocal relationship between the cytosolic signaling activated downstream to cytokines, ciliary architecture and the proteins that orchestrate ciliary trafficking. Primary cilia length and trafficking is altered by cytokines and the response of cells to cytokines is modified when ciliary trafficking and ciliogenesis is genetically interfered with. Signalling pathways such as NFkB are regulated in certain contexts by ciliary trafficking.
This has lead to the broad hypothesis that the primary cilium plays a key role in the tuning of the cellular signalling in physiological and disease settings where such signalling is abberantly activated and that if this is true such regulation may be exploitable.
Dr Wann's work seeks to establish the mechanism for ciliary influence over such signalling with a view to exploiting this to modulate cell behaviour in a variety of contexts. Another chief aim is to identify the importance of the cilium in adult tissues and in circumstances where tissue homeostasis is challenged triggering disease pathogenesis. The major current translational focus of this is towards arthritis, particularly osteoarthritis. Using a range of techniques from microscopy and molecular biology to pre-clinical pathogenesis models we aim to understand better the role of the primary cilum in a range of musculoskeletal contexts. The group is also interested, through collaboration, in the wider scope of the cilium’s putative role in other contexts where inflammatory signalling is important, from stem cell biology to diseases such as rheumatoid arthritis (synoviocytes) and ageing. We are currently also investigating roles for the cilium in peripheral neuron cytokine responses.
The work is currently supported by the Kennedy trust/ARUK fellowship, a Kennedy prize studentship, an ARUK centre of excellence initiative grant and Oxford University. Dr Wann is a KTRR/ARUK Fellow.