The Academic Vascular Surgery Research Unit was established in 2002 and has combined the research leadership of Dr Cockerill with the Surgical leadership of Professor Thompson to create a focused research group with the following expertise and facilites :
Expertise:
(1) In vivo models and cell research: We have established two powerful aneurysm models (the Angiotensin-induced and the Calcium-Chloride induced models) and have colonies of hypercholesterolaemic mice (ApoE deficient/C57BL6) in which all endothelial cells are labelled with a beta-galactocidase reporter construct or in which all cells are labelled thus. Members of this team share many skills in cell and molecular biology. Dr De Souza has a sound background in proteomics, having studied with Professor Mike Dunn
(2) Patient Recruitment and collection of human material for research. The Department of Vascular Surgery, St George’s Hospital provides access to clinical material from open repair and endovascular repair. The Department, lead by Professor Matt Thompson, has 8 consultants and has one of the largest aneurysm practices in the UK.
Facilities description: (i) Biological Research Facility- offering breeding of transgenic animals, and imaging (MRI and Infrared imaging systems) (ii) Biomics facility – offering proteomics, genomics, laser capture microscopy and gene chip analyses. (iii) Flow cytometry suit – providing facilities for dual and tri coloured staining and cell sorting.(iv) tissue culture suit – providing facilities for isolating progenitor cells and primary cultures (with isolated suites for human and animal work) (v) human tissue storage- providing facilities which meet GLP,GCP and HTA requirements.(vi) Clinical trials Unit –providing support for administration of clinical trials.
Tasks in FAD:
Replication analysis, following the genome-wide linkage and association studies, will be performed in patients recruited from the national screening programme.
Using bone marrow chimeric animals we will investigate the role of bone marrow-derived stem cells in the development of aortic aneurysms.
Using two animals models of aortic aneurysm we will establish the mechanism whereby thiazolidinediones (TZDs) inhibit formation and rupture of these lesions.
Using co-expression of CD34 and CD133 on peripheral blood mononuclear cells to identify and measure the number of progenitor cells in the blood, we will evaluate the use of such measures as a diagnostic tool for the disease and a marker of growth, by correlating to aneurysm size.
Serum samples will be colleted from men with aneurysms and age matched controls and biomarkers will be identified by comparative analysis of these two populations using DIGE/2D-PAGE.
Members of the FAD staff
| Cockerill GW | (PhD) | cell biologist, molecular biologist, in-vivo models | (WP3,4,5) |
| Thompson MM | (MD,FRCS) | surgeon | (WP3,5) |
| Loftus IM | (MD,FRCS) | surgeon | (WP3,5) |
| Torsney E | (PhD) | cell biologist, histopathologist | (WP3) |
| De Souza AI | (PhD) | biochemist, proteomics, bioinformatics | (WP3) |
| Hafez H | (FRCS) | surgeon | (WP2) |
| Steve Humphries | (PhD) | geneticist | (WP2) |
Main publication linked to FAD tasks
Choke E, Thompson MM, Dawson J, Wilson WR, Sayed S, Loftus IM, Cockerill GW. Abdominal aortic aneurysm rupture is associated with increased medial neovascularisation and overexpression of proangiogenic cytokines. Arterioscler Thromb Vasc Biol 2006. 26:2077-2082.
Joe Dawson, Jenny Tooze, Gillian Cockerill, Edward Choke, Ian Loftus, Matt Thompson. Endothelial progenitor cells and abdominal aortic aneurysms. NY Acad Sci 2006.1085;327-330.
Torsney E, Mandal K, Halliday A, Jahangiri M, Xu Q. Characterisation of progenitor cells in human atherosclerotic vessels. Atherosclerosis.2007;191:259-264.
Wilson WR, Anderton M, Schwalbe EC, Jones JL, Furness PN, Bell PR, Thompson MM. Matrix metalloproteinase-8 and -9 are increased at the site of abdominal aortic aneurysm rupture. Circulation.2006;113:438-445.
De Souza AI, Wait R, Mitchell A, Banner NR, Dunn ML, Rose ML.Heat shock protein 27 is associated with absence of graft vasculopathy after cardiac transplantation. Circulation Research 2005;79:192-198.