Meet Professor Ken MacLeod: Head of Section with NHLI

Professor Ken MacLeod is head of the Cardiac Function Section at the National Heart and Lung Institute (NHLI).

Professor Ken MacLeod studied at the Universities of Aberdeen and Edinburgh in Scotland, followed by two years at the University of California in the laboratory of Don Bers. Here he acquired an interest in the mechanisms underlying cardiac excitation-contraction coupling which led him into his current field of research. Professor MacLeod took over as Head of the Cardiac Function Section in 2018, and is also the Director of Conduct in the School of Medicine and chairs the Student Monitoring Group.

"Good educators work with their existing knowledge, but also incorporate the latest research in their field that nurtures enthusiasm and provides inspiration for young people" Professor Ken MacLeod

Professor MacLeod's research explores the processes that control cardiac cell contraction in health and disease. Investigation of these processes are fundamental to our understanding of the workings of the heart, will allow a more logical approach to therapy and, in the longer term, may provide impetus for a generation of new treatments.The Cardiac Function Section's research echoes Ken's interests as they look to understand how changes to the function of the constituent cells of the heart can lead to disease.

I caught up with Professor Ken MacLeod to find out more about him and his research.

What is your research about?

My own research examines the processes that control contraction of the heart in health and disease. My group studies these processes at various levels from the single cell to the whole heart using an array of physiological and biophysical techniques. We have a particular interest in exploring molecular and cellular mechanisms that can cause arrhythmias in the heart. 

What is your most exciting project at the moment?

The prevalence of cardiovascular diseases, particularly heart failure, increases with age in both men and women, but shows a more prominent increase in women older than 50 years. Part of the underlying reason has been thought to be due to a decline in oestrogens around menopause but distinguishing between the effects of the menopause per se, biological ageing processes and co-morbidities is challenging. There are large knowledge gaps and contradictory findings. We are about to publish a paper in which we describe not only global changes occurring in response to oestrogen supplementation in heart failure, but also concurrent alterations to cardiac muscle cell intracellular Ca²⁺ and Na⁺ regulation. To our knowledge this is the first time such studies have been described and they suggest that oestrogen can modulate ventricular myocyte remodelling responses to heart failure and more specifically, the function of proteins involved in intracellular ionic regulation. 

On the more “techie” side – and illustrative of the scientific interactions on our doorstep – we are collaborating with the Photonics Group in Imperial to construct and use a novel light-sheet fluorescence microscope system that can probe subcellular events at a new higher resolution. We are using this to study how intracellular Ca²⁺ release events may propagate to produce arrhythmias. 

There have been media reports of how research focuses on men, any comment on the importance of understanding women's health?

While there has been appropriate representation of women in more recent trials of hypertension and atrial fibrillation therapies, historically there has been under-representation of women in clinical trials for heart failure (HF) and coronary heart disease.  We are now learning that there are marked sex differences in various forms of HF but our knowledge of the underlying mechanisms that give rise to the sex specificity is very limited. Men predispose to HF with reduced ejection fraction (HFrEF), in contrast to women who tend to suffer more from HF with preserved ejection fraction (HFpEF). Sex differences are also found in a variety of cardiomyopathies (Takotsubo or stress-induced, chemotherapy-induced and some in which there is variable genetic penetrance of muscle protein mutations), and more obviously, in the rarer sex-specific condition of peripartum cardiomyopathy. While there is now better awareness of sex differences in HF, treatment guidelines tend to be based on male data.  It is important we understand how the sex differences occur so treatments can be more appropriately targeted. 

What is on the horizon for your Section?

A general description of the work of the Section is understanding how changes to the function of the constituent cells of the heart lead to the clinical manifestations of disease, but this barely indicates the wealth and diversity of expertise within it. The Section members always have exciting projects underway or in development. 

Our Section brings together people with scientific and clinical backgrounds who have a breadth of expertise in life sciences and they have strong interdisciplinary collaborations with Bioengineering, Computing, Physics, and Materials departments in Imperial and with outside institutions. We are using this knowledge to improve diagnostic procedures, provide better clinical management and generate novel treatments.  We have a strong research pipeline into regeneration studies (we are a BHF Cardiovascular Regenerative Medicine Centre) that are always exciting and push the boundaries of understanding, and a very active electrophysiology portfolio that encompasses studies of ion channels, electrical events in single cells, tissue slices and whole heart and investigation of complex arrhythmogenesis using novel mapping techniques and machine learning.

Have you been involved in any aspects of NHLI outside of research?

My involvement in teaching undergraduate medicine stretches back many years. I ran the MB ChB Cardiovascular course for about 12 years, taught and examined on the BSc Cardiovascular course and was Head of Assessment for Year 4. University education is constantly changing and is very different to the one I experienced as an undergraduate. We now need to be sufficiently agile to adapt curricula and methods of teaching to meet the needs of new undergraduate medical education and its policy-makers, while delivering the highest quality possible. Those last three words are important. Students tend to choose a university because it is highly ranked in league tables or has a strong reputation and these accolades mostly reflect the university’s research, not necessarily its teaching. It is vital we strive to produce the best educational experience that we can. It is all too easy to provide (and regurgitate) rather mundane teaching - good educators work with their existing knowledge, but also incorporate the latest research in their field that nurtures enthusiasm and provides inspiration for young people.

I am Director of Conduct in the School of Medicine and I chair the Student Monitoring Group that oversees all aspects of undergraduate student conduct, professionalism and health in relation to fitness to practise medicine.  It is an interesting job that presents a variety of cases that need robust, supportive, consistent and fair handling. Seeing and interacting first hand with the people involved in delivering and managing the whole medical curriculum has been an enlightening experience. The care, dedication and thoughtfulness of both the academic staff and the faculty education office staff is uplifting and enriching. 

Why did you become a scientist?

Curiosity. I like to understand how “stuff” works. Stuff can be anything; cells, organs, instruments, machines. Physiology is the study of how living organisms work. When I was a kid I would rarely read fiction, it sounds a bit geeky, but I was happiest reading encyclopaedias and similar general knowledge books. When I was doing my PhD I realised that academia was where I needed to be because of the freedom for investigation that it provides. Academic freedom is crucial for progress and understanding how things work in all facets of life. Universities must safeguard it. 

What or who inspires you?

There are too many people I find inspiring and some are at Imperial so I will not list them and I’ll go with “what”. The “what” is the environment. I consider myself very fortunate to work in an environment filled with very bright people. Their creativity, meticulousness and inventiveness inspires in my own work.   

What do you do to relax?

I played a lot of different sports in my early life and I continue to play some, though admittedly not at the same pace. Sport is a great leveller.  You meet people from different backgrounds, different professions and with a variety of ages. I don’t play rugby or cricket any more but I did coach both sports for about 20 years. It is important we encourage youngsters to play sport. It helps them develop into productive, happy, well-adjusted members of society because sport is a wonderful training ground for life's challenges. I now play tennis and golf most weeks and in the winter my wife and I ski as much as we can (afford!). We both learnt to ski from an early age and it is something we still enjoy. I also like cooking and making bread - by hand, not with a bread maker - and pasta.