Current Roles

Since 2001, John Danesh has been the Professor of Epidemiology and Medicine and Head of the 330-person Department of Public Health and Primary Care at the University of Cambridge. He is also Director of the Strangeways Research Laboratory, Director of the Cardiovascular Epidemiology Unit, and Honorary Consultant in Epidemiology for the Cambridge University Hospital NHS Foundation Trust.

Departmental Role

Professor Danesh has overseen major expansion in recent years of the Department of Public Health and Primary Care, which is one of Europe’s leading university departments of population health sciences. The department was top-ranked in Epidemiology and Public Health in the UK Research Assessment Exercise 2001-2008. Major developments in the department in recent years have included:

• establishment of a Centre for Genetic Epidemiology in 2003
• establishment of the MRC Centre for Nutrition and Cancer in 2006
• partnership in the National Institute for Health Research School for Primary Care Research since 2006
• establishment of major research initiatives in developing countries, and partnership in the Public Health Foundation of India-UK Consortium from 2008
• establishment of major collaborations with several industrial partners
• establishment of a new MPhil course in Public Health in 2006, and co-direction of a new four-year interdisciplinary PhD programme in cardiovascular research supported by the British Heart Foundation from 2009
• establishment of a new Behavioural Research Unit in 2010.

Background

John Danesh trained in medicine at the University of Otago in New Zealand and at the Royal Melbourne Hospital in Australia. As a Rhodes Scholar, he trained in epidemiology at the London School of Hygiene and Tropical Medicine and at the University of Oxford. He was elected to his present position at the University of Cambridge in 2001. He was awarded Fellowship of the Royal College of Physicians of London in 2007 and of the Faculty of Public Health, London in 2009. In 2011, he was awarded a European Research Council Advanced Investigator Award.

Research Interests

Professor Danesh leads a research group of over 50 staff and students and is an international leader in cardiovascular disease epidemiology, focusing on genetic, biochemical and lifestyle factors. He has authored over 130 publications, over 60 of which have appeared in leading clinical (eg, NEJM, JAMA, Lancet), scientific (eg, Nature, Nature Genetics) and specialty journals (eg, Circulation, Am J Epidemiology). These publications have attracted a total of over 10,000 citations to date. He is PI (or Joint PI) of several major international research projects, such as the 2 million person Emerging Risk Factors Collaboration, EPIC-CVD, and the Pakistan Risk of Myocardial Infarction Study.

Key Findings

The work of the Cardiovascular Epidemiology Unit (CEU), led by Professor Danesh, has had a considerable impact on public health, clinical guidelines, and priorities for medicines development in cardiovascular disease in the following main areas:

Lipids The CEU has demonstrated that lipid assessment can be greatly simplified by measurement of HDL and total cholesterol without the need to fast and without regard to triglyceride (JAMA 2009;302:1993-2000), with implications for simplified screening of millions of adults screened for CVD. Using large-scale genetic evidence, the CEU has shown that triglyceride-mediated pathways are causally relevant to coronary disease, probably acting through high VLDL concentration and/or HDL particle size (Lancet 2010;375:1634-9). The CEU has shown that apolipoprotein E genotypes are analogously and linearly related to both LDL-cholesterol levels and coronary risk (JAMA 2007;298:1300). The CEU’s work on triglyceride and HDL-C levels (and genetic variants related to these pathways, eg: JAMA 2008;299:2777-88) and cardiovascular disease has been cited by the 2011 guidelines of the European Atherosclerosis Society consensus panel for therapeutic targeting of patients with elevated triglycerides and/or low HDL-C.

Lipoproteins The CEU has shown that lipoprotein-associated phospholipase A₂ is log-linearly associated with risk of CVD, independent of established lipids (Lancet 2010;375:1536–44). This work has encouraged GlaxoSmithKline to launch a £250M programme of phase III trials of darapladib and it has been cited by the 2010 guidelines of the American College of Cardiology Foundation / American Heart Association Task Force recommending assessment of mass concentration of Lp-PLA₂ for targeted cardiovascular disease risk assessment. Danesh’s early work on lipoprotein(a) helped revive interest in this hypothesis (Circulation 2000;102:1082–85), and, more recently, the CEU has shown that lipoprotein(a) is specifically, continuously and independently associated with risk of CVD in a manner consistent with causality (JAMA 2009;302:412-423). This work has been cited by the 2010 guidelines of the European Atherosclerosis Society recommending Lp(a) for use in cardiovascular disease risk assessment.

Metabolism The CEU’s work has shown that diabetes and dysglycaemia are independently associated with premature death from a range of non-vascular conditions, including several major cancers, infectious diseases, degenerative diseases, injury, and suicide (NEJM 2011;364:829-841). The CEU has shown that diabetes confers 2-fold risk for a wide range of vascular diseases, but little of the link is explained by conventional risk factors (Lancet 2010;375:2215-2222). The CEU has demonstrated that clinical measures of adiposity do not add to cardiovascular risk prediction when information exists on lipids, blood pressure, and diabetes (Lancet 2011;377:1085-95). The CEU has co-led the discovery of 5 novel loci in type 2 diabetes among South Asians (Nat Genet in press).

Chronic infection & inflammation Danesh’s work on chronic infection has discouraged use of antibiotics to prevent CVD and yielded innovative approaches for evidence synthesis (Lancet 1997;350:430–36, JAMA 1998;279:1477–82). In powerful and detailed analyses, the CEU has shown that C-reactive protein (NEJM 2004;350:1387–97, Lancet 2010;375:132-40) and fibrinogen (JAMA 2005;294:1799-1809) are unlikely to be independent causal risk factors for CVD. However, the CEU has co-led the discovery of 9 novel loci in coronary disease (Nat Genet 2011;43:339-44; PLoS Genetics in press), including genes believed to be inflammation-related.

Funding

The CEU group has attracted about £50 million in external research funds in recent years from a variety of sources, including: the British Heart Foundation, the UK Medical Research Council, the European Commission, the European Research Council, the Wellcome Trust, US National Institutes of Health, UK National Institute of Health Research, several industry sources, and other funding agencies.

Advisory Roles

Professor Danesh chairs UK Biobank’s Outcomes Working Group and is a member of the UK Biobank Steering Committee. He is deputy chair of the Wellcome Trust’s Investigator Award Expert Review Group on Genetics/Genomics/Population Research. He serves on several editorial boards, eg: PLoS Medicine, European Journal of Epidemiology, Human Genomics, and international advisory boards for industry, eg: Novartis, Merck, BioScale. He has served on several major funding panels, eg: Wellcome/NIHR Health Innovation Challenge Fund, MRC Biomarkers, BHF, Genome Canada.

Career and Training Possibilities

Please contact Professor Danesh’s PA Hannah Sneath to find out more about research and training opportunities in his group and department (see top of page for contact details).