Research Profile
Dr Graham Standen
The process of blood clotting involves a complex
interaction between vascular endothelium, blood clotting factors and circulating platelets. Inherited defects of the components of the clotting cascade can lead to bleeding disorders e.g. haemophilia and von Willebrand's disease. In the steady state, a number of inhibitory factors have also been identified which act as so-called natural anticoagulants (e.g. antithrombin III, protein C) and prevent activation of the system. Inherited deficiency of these factors can result in inappropriate clotting and thrombotic disease.
We are interested in the molecular genetics of disorders of blood coagulation. We are exploring the mutational spectra in coagulation factor genes and, in collaboration with Professor Mike Tanner in the Department of Biochemistry, analysing the structure-function consequences of the mutations by molecular modelling of the mutant proteins and expression studies in yeast. We are also interested in the development of novel, rapid DNA techniques for diagnosis of these disorders in clinical practice.
References
Standen, G.R. and Bowen, D.J. (1993) Factor XIII A Bristol 1: detection of a nonsense mutation (Arg 171 → stop codon) in factor XIIIA subunit deficiency. Brit. J. Haem. 85, 769-772.
Aslam, S., Poon, M-C., Yee, V., Bowen, D.J. and Standen, G.R. (1995) Factor XIIIA Calgary: a candidate missense mutation (Leu667Pro) in the beta barrel 2 domain of the factor XIIIA subunit. Brit. J. Haem., 91, 452-457.
Wood, N., Standen, G.R., Bowen, D., Cumming, A., Lush, C., Lee, R. and Bidwell, J. (1996) UHG-based mutation screening in type 2B von Willebrands disease: detection of a candidate mutation Ser547Phe. Thrombosis and Haemostasis, 75, 363-367.
Aslam, S., Bowen, D., Mandalaki, T., Gialeraki, R. and Standen, G.R. (1996) Factor XIII deficiency due to a 13 base pair deletion in exon III of the A subunit gene. Am. J. Haematol. 53, 77-80.
Foley, P.W.X., Irvine, C.D., Standen, G.R., Morse, C., Smith, F.T., McGrath, C., Baird, R.N.F. and Lamont, P.M. (1997) Activated protein C resistance, Factor V Leiden and peripheral vascular disease. Cardiovasc. Surgery 5, 157-160.
Culpan, D., Standen, G.R., Wood, N., Mazurier, C., Gaucher, C. and Bidwell, J. (1997) Rapid mutation screening in type 2A von Willebrand's disease using universal heteroduplex generators. Brit. J. Haematol. 96, 464-469.
Bowen, D.J., Standen, G.R., Granville, S., Wood, N., Bidwell, J. (1997) Genetic diagnosis of Factor V Leiden using heteroduplex technology. Thrombosis and Haemostasis 77, 119-122.
Aslam, S., Yee, V., Narayanan, S., Duraisamy, G., Standen, G.R. (1997) Structural analysis of a missense mutation (Val414Phe) in the catalytic core domain of the factor XIIIA subunit. Brit. J. Haem. 98, 346-352.