Department of Cardiovascular Sciences

Genomics

Current research

Members

Genetics of CAD

We have one of the foremost groups undertaking cardiovascular genetics research in the UK and internationally. Three major projects all funded through programme grants underpin this research: The BHF Family Heart Study, The British Genetics of Hypertension (BRIGHT) Study and The Genetic Regulation of Arterial Pressure of Humans in the Community (GRAPHIC) Study.

Using these and other resources we have contributed to internationally leading research in the field of cardiovascular genetics. Perhaps most notable is the involvement of both the BHF Family Heart Study and the BRIGHT study in the ground-breaking Wellcome Trust Case Control Consortium (WTCCC) project, which investigated the genetic basis of seven common diseases using a genome-wide association approach, reporting in 2007 (Nature 2007; 447:661–678). Professor Nilesh Samani is a member of the WTCCC Management Committee and PI for the CAD component. Ongoing work has included looking at the role of copy number variants, concluding that these do not contribute to the risk of common diseases including coronary artery disease and do not explain a significant proportion of the missing heritability of these diseases (Nature 2010; 464:713-20). In other international collaborative studies, we identified 8 new loci that affect blood pressure and risk of hypertension that contain genes which have hitherto not been implicated in blood pressure regulation and thus provide novel targets for future treatments (Nat Genet 2009; 41: 666-676.). More recently, as part of the CARDIoGRAM consortium (co-led by Professor Nilesh Samani), we identified 13 new loci for coronary artery disease (Nat Genet 2011; 43:333-338). Our work in this field was further recognised by the award of a European Union FP6 Integrated Project, Cardiogenics (2006-2010) which took the genome-wide association signals forward into functional and translational studies. Other highlights include identification of the first human genetic variant that associates with telomere length, a marker of biological ageing (Nat Genet 2010; 42: 197-9). The findings could have important implications for our understanding of common age-associated diseases such as heart disease and cancer.

The clinical studies are complemented by studies in experimental models through a Wellcome Trust Cardiovascular Functional Genomics Programme Grant (2003-2009). Specifically, we have mapped and extensively investigated a major quantitative trait locus regulating blood pressure (BP) on rat chromosome 1 using a range of approaches including gene knock-out, renal transplantation and microarray expression profiling.

Platelet Biology and Haemostatic Mechanisms

Normal haemostasis depends on the interaction of platelets, coagulation factors and other blood cells. This area, led by Professor Alison Goodall, is principally directed towards an understanding of the factors that affect inter-individual variation in haemostatic mechanisms, and overlaps with the programme  in Cardiovascular Genetics and Genomics specific areas of interest include the understanding of the regulation of the platelet haemostatic response, in which platelets, and platelet-derived microparticles support the generation of thrombin. Platelet-derived microparticles also convey a range of molecules to other cells and this forms part of a research programme into the interaction of platelets, and platelet-derived factors, such as oxylinins and microRNA, “talk” to other blood cells (especially monocytes) and regulate gene expression.

The platelet programme also includes clinical studies, for example investigating the relationship between platelet responsiveness and the functional and clinical efficacy of anti-platelet drugs. We have recently taken part in a European Union FP7 Integrated Project; PRESTIGE (2010-2014) to investigate the causes and potential prevention of stent thrombosis in coronary artery disease patients and we currently have a collaboration with Astra Zeneca to investigate the effect of the P2Y12 antagonist ticagrelor in preventing cancer metastases

Professor Goodall is also a Founding Director of a University of Leicester Spin-out company, Haemostatix Ltd. that has developed first-in-class clotting agents for the treatment of bleeding and has recently been acquired by Ergomed PLC.

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