Research groups

Research

Regulation of intracellular traffic and the actin cytoskeleton by Rho family GTPases.

Rho GTPases act as molecular switches that control a wide range of signalling pathways in mammalian cells. Over twenty different Rho family members have been identified so far, but only three have been studied in detail – RhoA, Rac1 and Cdc42. These have been shown to be critical controllers of cell shape and cell movement through their regulation of the actin cytoskeleton.

We are working to understand the functions of the novel Rho GTPases, which we think will turn out to be as interesting as the big three family members. To do this we combine the use of cell signalling studies with a wide range of cell imaging techniques such as confocal microscopy and time-lapse microscopy of Rho GTPases in living cells. We find that many of the novel Rho GTPases have functions in specialised human cells and tissues, and for most of our current work we use primary human cells, which we believe will give us a more accurate picture of the physiological functions of these signalling proteins.

Confocal image of RhoB+ endocytic vesicles in cells treated with or without the novel cancer therapeutic L-744832

Through this work, we have become interested in the roles that Rho GTPases play in normal and pathological human physiology and our current studies look at the functions of Rho GTPases in cancer, immune function and angiogenesis. We think that by studying Rho GTPase function in these very 'real' contexts that we can get to a deeper understanding of the fundamental cell biology behind these signalling proteins, as well as contributing to clinical research in these areas.

Group

Chris Cowell, Lifei Fan, Clare Hetheridge, Caroline McKinnon, Alice Scott.

Recent publications

Fan L, Pellegrin S, Scott A and Mellor H. (2010) The small GTPase Rif is an alternate trigger of actin stress fiber formation in epithelial cells. J Cell Sci. In press

McKinnon CM, Lygoe KA, Skelton L, Mitter R and Mellor H. (2008) The atypical Rho GTPase RhoBTB2 is required for expression of the chemokine CXCL14 in normal and cancerous epithelial cells. Oncogene 27, 6856-6865.

Scott A, Hetheridge C, Reynolds A, Nayak V, Hodivala-Dilke K and Mellor H. (2008) Farnesyltransferase inhibitors target multiple endothelial cell functions in angiogenesis. Angiogenesis 11, 337-346.

Gampel A, Moss, L, Jones, JC, Norman JC, Brunton, V and Mellor, H. (2006) VEGF regulates the mobilisation of VEGFR-2/KDR from an intracellular endothelial storage compartment. Blood 108, 2624-2631.