Home| Lecturer in Cell Biology |
Contact details:
| Tel: | +44 20 7882 2359 |
| Fax: | +44 20 7882 2186 |
| Email: | m.d.turner@qmul.ac.uk |
| Address: |
Centre for Diabetes, |
Biography
Dr. Turner obtained his B.Sc. (Hons) in Biochemistry at the University of Dundee, UK, before going on to obtain his PhD in Physiology at the University of Liverpool, UK studying the molecular mechanisms of secretion from lactating mammary epithelial cells within the laboratory of Prof. Robert D. Burgoyne. In order to widen his horizons, whilst still pursuing his interest in endomembrane transport, he spent 6 years training as a post-doctoral research associate in the USA, working first with Prof. William E. Balch at The Scripps Research Institute in La Jolla, CA identifying biochemical factors mediating assembly of the endoplasmic reticulum, and then with Prof. Peter Arvan at Harvard Medical School, Boston, MA, and Albert Einstein College of Medicine, Bronx, NY investigating mechanisms of protein sorting, storage and maturation in the late secretory pathway of pancreatic b-cells.
Dr. Turner returned to the UK in 2000 to take up a faculty position at Barts & The London School of Medicine & Dentistry. Here he has continued to develop his interest in protein trafficking, notably determining how calpain-10 regulates insulin secretion through partial proteolysis of SNAP-25, an essential core component of the secretory granule fusion machinery in pancreatic b-cells. More recently he has also developed an avid interest in the mechanisms triggering apoptosis and inflammation, both in pancreatic islets exposed to diabetogenic levels of glucolipotoxicity and also in the auto-inflammatory disease TNF receptor associated periodic syndrome (TRAPS). His particular interests within this area revolve primarily around cell signalling events associated with members of the TNF receptor superfamily.
In addition to his current research activity, Dr. Turner is also a member of the Editorial Boards of Biochimica Biophysica Acta – Molecular Cell Research, and Bioscience Reports. He is also a well known figure within the Biochemical Society, being a current member of the Meetings Board and a former Member of Council. In addition he was previously an elected member of Barts & The London, School Board.
Research Activity
Calpain-10
Defects in the gene encoding calpain-10 result in increased susceptibility to development of type 2 diabetes. My group is interested in discovering the mechanisms of action of calpain-10 at the cellular level. We have recently shown that calpain-10 proteolyses SNAP-25, a key component of the insulin secretory granule fusion complex. We are now seeking to further understand its role in exocytosis, and also other areas of the secretory pathway including the cytoskeleton.
Protein Trafficking
The regulated secretion of hormones such as insulin requires efficient transport along a series of discreet organelles that comprise the secretory pathway. My group is particularly interested in how secretory protein is effectively sorted and packaged into secretory vesicels/granules.
TNF Receptor Cell Signalling and Type 2 Diabetes
TNF receptor mutations result in the development of a large number of inflammatory diseases, and we have recently discovered a specific mutation that is associated with type 2 diabetes. We are currently investigating the effect that this mutation, and TNF receptor mutations in general, have upon NFkappaB signalling pathways.
Glucolipotoxicity
Type 2 diabetes is characterised by elevated circulating levels of glucose and lipids. We are currently studying how these factors (and one of the drugs commonly used to treat hyperglycaemia) effect insulin secretion and beta cell survival, using a combination of microarray technology and traditional molecular cell biology techniques.
Key Publications
• Dominguez,V., Raimondi,C., Somanath,S., Bugliani,M., Loder, M.K., Edling,C.E., Divecha, N., da Silva-Xavier,G., Marselli, L., Persaud, S.J., Turner,M.D., Rutter, G.A., Marchetti, P., Falasca,M., and Maffucci,T. (2010). Class II phosphoinositide 3-kinase regulates exocytosis of insulin granules in pancreatic beta cells. J. Biol. Chem. In press (doi:10.1074/jbc.M110.200295).
• Nedjai,B., Hitman,G.A., Quillinan,N., Coughlan,R.J., Church,L.D., McDermott,M.F. and Turner,M.D. (2009). Proinflammatory action of the antiinflammatory drug infliximab in TNF-receptor associated periodic syndrome. Arthritis Rheum. 60, 619-625.
• Nedjai,B., Hitman,G.A., Yousaf,N., Chernajovsky,Y., Stjernberg,S., Pettersson,T., Ranki,A., Hawkins ,P., Arkwright,P.D., McDermott,M.F. and Turner,M.D. (2008). Abnormal TNFR1 cell surface expression and NF- k B activation in TNFR1-associated periodic fever syndrome (TRAPS). Arthritis Rheum. 58, 273-283.
• Aganna,E., Burrin,J.M., Hitman,G.A. and Turner,M.D. (2006). Involvement of calpain and synaptotagmin Ca 2+ sensors in hormone secretion from excitable endocrine cells. J. Endocrinol. 191, R1-7.
• Lara-Lemus,R.*, Liu,M.*, Turner,M.D.*, Scherer,P, Stenbeck,G., Iyengar,P. and Arvan,P. (2006). Lumenal protein sorting to the constitutive secretory pathway of a regulated secretory cell. J. Cell Sci.119, 1833-1842. (*Joint first authors).
• Marshall ,C., Hitman,G.A., Partridge,C.J., Clark ,A., Ma,H., Shearer,T.R. and Turner,M.D. (2005). Evidence that an isoform of calpain-10 is a regulator of exocytosis in pancreatic b -cells. Mol. Endocrinol. 19, 213-224.
• Yousaf,N., Gould,D.J., Aganna,E., Hammond,L., Mirakian,R.M., Turner,M.D., Hitman,G.A., McDermott,M. and Chernajovsky,Y. (2005). Tumor necrosis factor receptor I from patients with tumor necrosis factor receptor-associated periodic syndrome interacts with wild-type tumor necrosis factor receptor I and induces ligand-independent NF-kappaB activation. Arthritis Rheum. 52, 2906-2916.
• Turner,M.D. and Arvan,P. (2000). Protein traffic from the secretory pathway to the endosomal system in pancreatic b -cells. J. Biol. Chem. 275, 14025-14030.
• Turner,M.D., Plutner,H. and Balch,W.E. (1997). A Rab GTPase is required for homotypic assembly of the endoplasmic reticulum. J. Biol. Chem. 272, 13479-13483.
• Turner,M.D., Rennison , M.E. , Handel,S.E., Wilde,C.J., and Burgoyne,R.D. (1992). Proteins are secreted by both constitutive and regulated secretory pathways in lactating mouse mammary epithelial cells. J. Cell Biol. 117, 269-278.
