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Led by Professor Martin Bennett |
Professor Martin Bennett
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...will (i) identify new and relevant genetic and biomarkers of cardiovascular and pulmonary vascular disease and their progression using blood, tissue and novel imaging methods which will (ii) identify targets for new therapies and (iii) optimise existing therapies. Novel diagnostic approaches will underpin further stratification of treatment of atherosclerosis, atherothrombosis, systemic hypertension and pulmonary hypertension.
How the aims and objectives will be achieved:
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1. Atherosclerosis |
We have established a network of basic and clinical investigators to study atherosclerosis. In particular, we have determined the fundamental role of cell death and cell senescence in atherosclerosis (J Clin Invest 1995;95:2266-2274, Nat Med. 2006;12:1075-1080, Circ Res .2006;99:156-164 ), and identified many of the regulatory pathways (Science. 1998;282:290-293 )(Professor Bennett). We have also identified novel markers of atherosclerosis (Professor Bennett, Dr Catherine Shanahan, Dr Martin Goddard), developed a unique model of unstable atherosclerosis to test plaque stabilising drugs (Professor Bennett), and established novel FDG-PET imaging (Dr Elizabeth Warburton, Dr David Dutka) and NMR spectroscopy (Dr David Grainger) to detect atherosclerosis in the cerebrovascular and coronary circulations in patients.
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2. Atherothrombosis |
Collagen and thrombin are the two most potent platelet agonists, and activation via their signalling receptors results in thrombus formation. Collagen is released uponplaque rupture whilst thrombin results from activation of the coagulation cascade. TheCambridge atherothrombosis researchers include clinician-scientists (Dr Ouwehand), statisticians/ bioinformaticians (Dr Simon Thomson, MRC) and experts in cell signalling, collagen peptide chemistry (Dr Richard Farndale), structural studies (Dr James Huntington), protein engineering (Dr Ian Tomlinson, Domantis Ltd) and on model organisms (Dr Derek Stemple). Molecular and structural studies on collagen and thrombin complement genome-wide association studies and will determine the extent to which platelet gene sequence variation modifies the propensity to thrombus formation post plaque rupture.
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3. Pulmonary Hypertension |
We have identified the major cause of primary and sporadic PHT, namely defects in BMPR2 receptor signalling ( Hum Mol Genet. 2002;11:1517-1525) and PHT in hereditary telangiectasia, namely ALK-1 ( N Engl J Med. 2001;345:325-334, J Med Genet.40:865-871 (Dr Nicholas Morrell) . These studies have novel targets for PHT treatment and established the role of pulmonary vasodilator therapy to treat PHT (Dr Nicholas Morrell, Dr Joanna Pepke-Zaba).
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4. Systemic Hypertension |
Our research strategy utilises small crossover studies that highlight differences in response or phenotype between contrasting drugs, to tailor drug therapy to individual patients (Professor Morris Brown, Dr Ian Wilkinson).
Addenbrooke's Cardiology Services
Cardiovascular Medicine
Clinical Pharmacology
Respiratory Medicine
Platelet Genetics and Immunobiology
Papworth Hospital Services
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