Research in our division bridges an important gap between research and the clinic. We have an essential role in the translation of laboratory science into novel diagnostics and disease treatments.
During a heart attack, blockage of a coronary artery prevents blood flow to part of the heart, a condition termed ischaemia. As a result, the mitochondria in this tissue are deprived of oxygen and energy production stops. We have demonstrated that one of the mitochondrial fuels (succinate) builds up during ischaemia, but is consumed via an alternative mitochondrial route that does not produce energy and instead produces oxygen radicals that destroy the heart muscle. Because lost heart muscle cannot be regenerated the patient is left with a weakened heart and heart failure often re-occurs. To avert this, we identify therapies that reduce cell death in ischaemic hearts.
We also focus on the biological pathways responsible for arteriosclerosis, systemic hypertension and vasculitis with a strong emphasis on basic physiology, experimental medicine and early phase interventional clinical trials. This includes studying the impact of cardiovascular risk factors such as age, the response to novel drugs, and differences between different ethnic groups. It allows us to assess the causes of disease and develop novel biomarkers. In addition, a portfolio of studies on ANCA vasculitis has been co-ordinated from Cambridge over the last 25 years. These have defined the current standard of cares and informed systematic reviews and international consensus management guidelines. This has led to the first study of B cell depletion therapy in vasculitis which has resulted in subsequent Phase III studies and drug registration.
One third of all current medicines target G-protein-coupled receptors (GPCRs). Our work helps to understand the role of these in cardiovascular disease by using tissues obtained under ethical approval and informed consent at the time of surgery. The role of orphan GPCRs is also explored using model systems. These GPCRs were originally predicted from the human genome, but until recently were not paired with the molecules that activate them. Our identification of an analogue of these molecules has since been progressed to first in human studies. Other identified compounds are ideal as a laboratory tools and form the basis for new drugs that treat cardiovascular conditions, such as pulmonary arterial hypertension.
A major success of our division is our ability to advance our experimental work into the clinic. Our specialists develop clinical trial methodologies that include a portfolio of interventional clinical trials, cohort studies, biomarker identification, histopathology and clinical epidemiology. Our current research interests include innovative and efficient trial design, including multi-arm multi-stage trials, pragmatic trials (that monitor the benefits of routine clinical practice), and the use of routine data sources and eHealth technologies to capture trial endpoints and events. Some of these involve global networks with centres in countries such as North America, Australia, New Zealand and Japan.