BHF Intermediate Fellow and University Research Lecturer
My research revolves around metabolism and energy generation in the heart.
The heart has a large demand for ATP to fuel its continual contractile activity, which is generated by the metabolism of substrates such as fatty acids and glucose. Abnormalities in substrate metabolism have been identified in the majority of cardiac pathologies, and contribute to the development of the disease. Abnormal fuel utilisation results in ATP insufficiency, depletion of essential metabolic intermediates, generation of deleterious side products and ultimately cardiac contractile failure.
I joined the Department in 2003 as a DPhil student of Prof Kieran Clarke, having completed my undergraduate degree in Medical Biochemistry at the University of Surrey. My doctoral research investigated the role of abnormal substrate metabolism in the development of cardiac hypertrophy. It focused on the relationship between fatty acid metabolism and cardiac function, demonstrating a strong interrelationship between these two factors, and identified key sarcolemmal changes in fat transport that regulate this process.
My subsequent post-doctoral research focused on the role of mitochondrial metabolism and oxygen consumption in cardiac disease progression. This work identified changes in electron transport chain complexes in the very early metabolic changes following myocardial infarction. I have also shown that adaptation to chronic hypoxia involves control of electron transport within the mitochondria, but these regulated changes are beneficial steps for optimising cell survival when oxygen is limited.
In 2011 I was awarded a Diabetes UK RD Lawrence fellowship, to study the role of abnormal adaptation to hypoxia and metabolism in the type 2 diabetic heart. Heart disease is the leading cause of mortality in patients with type 2 diabetes, and patients have increased incidence of, and decreased recovery following myocardial infarction. I believe this is related to metabolic inflexibility of the heart in diabetes, which prevents the heart adapting to a fall in oxygen concentration, as occurs during a myocardial infarction and angina. This research combines in vivo and ex vivo techniques to investigate these changes, and employs pharmacological and systems biology approaches to identify potential therapeutic targets to treat the diabetic heart.
Bernard and Joan Marshall Awards at the autumn meeting of the British Society for Cardiovascular Research 2017.
Carr CA. et al, (2018), Heart, 104, 1383 - 1384
Fatty Acids Prevent Hypoxia-Inducible Factor-1α Signaling Through Decreased Succinate in Diabetes.
Dodd MS. et al, (2018), Jacc basic transl sci, 3, 485 - 498
The 'Goldilocks zone' of fatty acid metabolism; to ensure that the relationship with cardiac function is just right.
Kerr M. et al, (2017), Clin sci (lond), 131, 2079 - 2094
Inhibition of sarcolemmal FAT/CD36 by sulfo-N-succinimidyl oleate rapidly corrects metabolism and restores function in the diabetic heart following hypoxia/reoxygenation.
Mansor LS. et al, (2017), Cardiovasc res, 113, 737 - 748
Type 2 diabetic hearts are energetically defective, with dysfunctional mitochondria insensitive to regulation by fatty acids
Kerr M. et al, (2017), Diabetic medicine, 34, 25 - 25