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• genetics, genomics and molecular biology
• physiology and non-communicable disease
• Other - please suggest keyword(s):

• Medicine

• Cardiology
• Immunology
• Physiology

My lab is focussed on developing a greater understanding of the mechanisms that drive the pathogenesis of heart failure (HF) with particular interest in HF with preserved ejection fraction (HFpEF). The epidemic of HF is being driven by hypertension, obesity, and diabetes. Our goal is to develop therapeutic strategies that can be employed in at-risk patients to prevent the progression to symptomatic disease.

Current projects utilise models of cardiac stress (Hypertension, myocardial infarct, obesity, diabetes). From this work we have developed a new treatment for hypertrophic cardiomyopathy (European Patent Pending) and have developed a greater understanding of disease pathogenesis (Watson CJ. et al. J. Cardiovasc Pharmacol Ther 2016, Horgan SJ et al. J. Cardiovasc Transl Res. 2015).

We also have strong clinical collaboration with Prof Ken McDonald and are actively engaged in identifying biomarkers of cardiac dysfunction that will better identify patients at risk of developing heart failure. This collaboration also gives us access to patient-derived tissue and blood cells that we use to complement our studies (Collier P. et al. J Mol Cell Cardiol. 2012, Phelan D. et al. PLoS One 2012, Glezeva N. et al. J Card Fail. 2015).

Background
Our current work is focussing on the role of inflammation and fibrosis in driving cardiac dysfunction in the setting of heart failure (HF). The overarching hypothesis is that obesity and metabolic syndrome cause an exaggerated systemic inflammatory environment that exacerbates cardiac responses to stresses like hypertension.

A key underlying feature of modern diseases such as obesity, metabolic disease and HF is sedentary lifestyles. Poor diet (Western diet) has been linked with obesity and HF but it is unclear how diet affects cardiac injury. Research has focussed on the fat composition of diet but our proposal is that the fibre content of our diet plays a crucial role in regulating systemic inflammatory responses, and thus the cardiac response to injury, due to its effects on the gut microbiota.

The level of fibre in the diet has a profound effect on the gut flora and the type of fermentation products produced (Sonnenburg et al. Nature. 2016). High fibre diets (traditional diets) support the production of short chain fatty acids which in turn play an endocrine anti-inflammatory role in other organs such as the lung (Trompette et al. Nat Med. 2014).
The aim of this research programme is to assess the impact of dietary fibres and gut microbiota composition on cardiac responses to pressure overload. In addition we will sequence the gut microbiota from patients at various stages along the HF spectrum in order to identify disease and diet-associated changes.
The ultimate goal is to develop food-based interventions that will prevent the development of HF.

Project Outline
1. Sequence gut microbiota from patients with HF.
2. Isolate patient inflammatory cells for in vitro studies.
3. Assess impact of manipulating gut flora and diet on responses to cardiac stress in relevant in vivo models.