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Dr Adam Grieve

Dr Adam Grieve

Jones and Anson Junior Research Fellow in the Biosciences

Positions

The Jones and Anson Junior Research Fellow, Lincoln College

Marie Skodowska-Curie Fellow, Sir William Dunn School of Pathology

Qualifications

PhD (University College London)

Academic Background and Previous Positions

Upon completing my doctoral studies in London with Dr. Tim Levine, I joined the group of Dr. Catherine Rabouille at the Hubrecht Institute, the Netherlands where my interest in proteolysis began. After four years, I returned to the UK where I am currently working with Prof. Matthew Freeman in the Sir William Dunn School of Pathology. My primary line of research is membrane trafficking and proteolysis, with a focus on how these often intersecting processes regulate events such as intercellular signalling and adhesion, which are cellular behaviours that often go awry in disease. 

Research Interests

A high proportion of proteins are synthesised as transmembrane precursors that are subject to proteolysis. The liberation of their active ectodomains through cleavage can affect many processes: it can generate soluble signalling molecules, cause a change in adhesive properties, and also trigger subsequent protein degradation. Intramembrane proteases are major players in this process by cleaving substrates within the lipid bilayer. Misregulation of intramembrane protease activity has been implicated in several disease conditions such as cancer and neurodegeneration. The best-characterised and largest family of intramembrane proteases are the rhomboids, which are conserved throughout all kingdoms of life. To date, the study of active rhomboid proteases has utilised arbitrary cell lines, or model organisms such as yeast and flies. Therefore their physiological significance in mammals is largely unknown, as is the substrate-selectivity of most mammalian rhomboids. My major focus is the discovery of new substrates for the rhomboid protease family, which, in combination with studies with mammalian model systems, will reveal their physiological roles.

Publications

Grieve, A. G.+, & Rabouille, C.+ (2014). Extracellular cleavage of E-cadherin promotes epithelial cell extrusion. J Cell Sci, 127(Pt 15), 3331-3346. doi: 10.1242/jcs.147926

Siggs, O. M*., Grieve, A*., Xu, H.*, Bambrough, P., Christova, Y., & Freeman, M. (2014). Genetic interaction implicates iRhom2 in the regulation of EGF receptor signalling in mice. Biol Open, 3(12), 1151-1157. doi: 10.1242/bio.201410116

Veenendaal, T., Jarvela, T., Grieve, A. G., van Es, J. H., Linstedt, A. D., & Rabouille, C. (2014). GRASP65 controls the cis Golgi integrity in vivo. Biol Open, 3(6), 431-443. doi: 10.1242/bio.20147757

Grieve, A. G.*, Daniels, R. D.*, Sanchez-Heras, E., Hayes, M. J., Moss, S. E., Matter, K., . . . Levine, T. P. (2011). Lowe Syndrome protein OCRL1 supports maturation of polarized epithelial cells. PLoS One, 6(8), e24044. doi: 10.1371/journal.pone.0024044

Hayes, M. J., Shao, D. M., Grieve, A., Levine, T., Bailly, M., & Moss, S. E. (2009). Annexin A2 at the interface between F-actin and membranes enriched in phosphatidylinositol 4,5,-bisphosphate. Biochim Biophys Acta, 1793(6), 1086-1095. doi: 10.1016/j.bbamcr.2008.10.007

Reviews

Grieve, A. G., & Rabouille, C. (2011). Golgi bypass: skirting around the heart of classical secretion. Cold Spring Harb Perspect Biol, 3(4). doi: 10.1101/cshperspect.a005298

Vinke, F. P., Grieve, A. G., & Rabouille, C. (2011). The multiple facets of the Golgi reassembly stacking proteins. Biochem J, 433(3), 423-433. doi: 10.1042/BJ20101540

Giuliani, F.*, Grieve, A.*, & Rabouille, C. (2011). Unconventional secretion: a stress on GRASP. Curr Opin Cell Biol, 23(4), 498-504. doi: 10.1016/j.ceb.2011.04.005

Grieve, A. G., Moss, S. E., & Hayes, M. J. (2012). Annexin A2 at the interface of actin and membrane dynamics: a focus on its roles in endocytosis and cell polarization. Int J Cell Biol, 2012, 852430. doi: 10.1155/2012/852430

* = co-first author
+ = co-corresponding author



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