Dr Sarah Calaghan

Profile

I was appointed as a Tenure-track University Fellow at Leeds in 2006, becoming a lecturer in 2011 with promotion to Associate Professor in 2012.

During my postdoctoral career at Leeds I was supported by a British Heart Foundation Intermediate Fellowship, as well as British Heart Foundation project grants.

My PhD in the Pharmacology Department at Leeds focused on cardiac function in acute renal failure. After this I spent several years travelling the world.

Responsibilities

  • Cardiovascular Group Theme Lead

Research interests

The heart pumps blood around the body, delivering nutrients to and removing waste products from every organ. Its function is finely tuned to respond to the demands of the body. Much of my research focuses on the mechanisms which control the behaviour of individual cardiac muscle cells in the heart in response to a variety of stimuli. This information can be used to understand the function of the heart in both health and disease.

Physiologically, stretch of cardiac muscle (e.g. by an increase in venous return during exercise) and β-adrenergic signalling (sympathetic nervous system activation) are the most important mechanisms for regulation of cardiac function. In recent years we have come to understand that mechanotransductive and β-adrenergic signalling both depend on small pits in the cell membrane known as caveolae.

Caveolae (‘little caves’) are invaginated lipid rafts, around 100 nm in diameter. Caveolae can act as reservoirs of extra membrane that are incorporated into surface membrane when required (i.e. during stretch). However caveolae also have a key role as a signalling platform. The integral membrane protein caveolin is vital for the morphology of caveolae, but it also scaffolds and regulates numerous signal components. Surrounding the caveolae bulb is a network of cavin proteins. Together the caveolin and cavin proteins form the caveolar coat complex (CCC), recently described by several high profile groups.

Cavins and caveolae: Our recent work in cardiac cells in collaboration with Dr Will Fuller (Glasgow) has identified cavins as labile proteins, which accords with their peripheral location around the caveolar bulb. Cavins move to caveolae in response to β-adrenergic signalling. Our current work aims to characterise the CCC in the cardiac myocyte and describe the impact of mechanotransductive stimuli (stretch and swelling) on the patency of the coat.

Caveolae and disease: Understanding the remodelling of the failing heart with a view to reversing this is a major goal in heart failure treatment. Our on-going work is exploring how changes in caveolae may contribute to remodelling in both right and left ventricular models of heart failure.

Statins and muscle: Statins are the most widely prescribed drug in the Western world. Our interest in statins stemmed from the knowledge that caveolae are cholesterol-dependent structures and that statins inhibit cholesterol synthesis.  As statins are taken by many apparently healthy individuals (who are at risk of cardiovascular disease), the side-effects associated with this medication are the cause of much concern. Indeed most people discontinue treatment within 2 years. We are interested in myopathy (skeletal muscle pain and weakness) which is the major cause of poor compliance. Our on-going work has revealed mechanisms of statins effects on muscle and account for the skeletal muscle-specificity of these effects.

Statins and exercise: Exercise is recommended for those at risk of cardiovascular disease (i.e. those who take statins), however there are reports that exercise exacerbates statin myopathy. Using a custom-built voluntary exercise analysis system (developed in collaboration with Dr Andrew Weightman at the University of Manchester) we are studying the interaction of exercise and statin treatment.

<h4>Research projects</h4> <p>Any research projects I'm currently working on will be listed below. Our list of all <a href="https://biologicalsciences.leeds.ac.uk/dir/research-projects">research projects</a> allows you to view and search the full list of projects in the faculty.</p>

Qualifications

  • BSc, PhD 1991, Leeds.

Professional memberships

  • Physiological Society

Student education

I teach at all levels on the BMS programmes.

<h4>Postgraduate research opportunities</h4> <p>We welcome enquiries from motivated and qualified applicants from all around the world who are interested in PhD study. Our <a href="https://biologicalsciences.leeds.ac.uk/research-opportunities">research opportunities</a> allow you to search for projects and scholarships.</p>