Investigating sex differences in heart failure

Summary The Cardiac Phenomics Laboratory research is about understanding how the heart response to stress can be managed to minimize the damaging impacts of a variety of disease conditions. We investigate responses of the working ‘pumping’ heart, of specialized muscle tissues and cells from different regions of the heart and of molecular signaling processes. As our name suggests, we look at how the cardiac ‘genome’ (the genetically defined heart) is translated in different stressor situations to create the ‘phenome’ (the structurally and functionally defined heart). Our pre-clinical work focuses on cardiac pathology arising from Type 1 and Type 2 diabetes and on the factors which determine how female and male hearts respond differently to stress and disease challenges. These areas of heart health are of critical significance in shaping the demographics of cardiovascular disease. We use experimental models to mimic human disease conditions, and we look for links between the performance of single muscle cells and the functioning heart. Our goals are to inform the development of new treatments for diabetic cardiomyopathy and to understand how for women and men, cardiac ‘difference’ may be managed with optimized therapeutic tools.Student projects in the Cardiac Phenomics lab could incorporate a range of methodologies including animal dietary and pharmacologic treatments, instrumented working heart preparations, immunohistochemistry, cell culture and adenoviral expression manipulation, cell kinetic imaging, biochemical assay, confocal microscopy, microarray gene profiling, realtime PCR, and western blot techniques. Projects are particularly suitable for MSc students, as there is scope for progression to publication within the degree time frame and research work is supported by complementary skills development coursework.

Project Details

The Cardiac Phenomics Laboratory research is about understanding how the heart response to stress can be managed to minimize the damaging impacts of a variety of disease conditions. We investigate responses of the working ‘pumping’ heart, of specialized muscle tissues and cells from different regions of the heart and of molecular signaling processes.  As our name suggests, we look at how the cardiac ‘genome’ (the genetically defined heart) is translated in different stressor situations to create the ‘phenome’ (the structurally and functionally defined heart). Our pre-clinical work focuses on cardiac pathology arising from Type 1 and Type 2 diabetes and on the factors which determine how female and male hearts respond differently to stress and disease challenges. These areas of heart health are of critical significance in shaping the demographics of cardiovascular disease.  We use experimental models to mimic human disease conditions, and we look for links between the performance of single muscle cells and the functioning heart. Our goals are to inform the development of new treatments for diabetic cardiomyopathy and to understand how for women and men, cardiac ‘difference’ may be managed with optimized therapeutic tools.Student projects in the Cardiac Phenomics lab could incorporate a range of methodologies including animal dietary and pharmacologic treatments, instrumented working heart preparations, immunohistochemistry, cell culture and adenoviral expression manipulation, cell kinetic imaging, biochemical assay, confocal microscopy, microarray gene profiling, realtime PCR, and western blot techniques. Projects are particularly suitable for MSc students, as there is scope for progression to publication within the degree time frame and research work is supported by complementary skills development coursework.

 Heart failure with preserved ejection fraction (HFpEF) accounts for more than 50% of heart failure patients and is particularly prevalent in women. An understanding of the cellular mechanisms underlying HFpEF is limited with no clincial treatments identified. In particular, gender-specific aspects of HFpEF etiology have not been well characterised. There are few animal models of HFpEF currently available and those that are utilised generally investigate male animals only.   We have used our unique model of HFpEF to produce preliminary experimental evidence which suggests that the cellular mechanisms underlying this disease are different in males and females. This project will expand and extend these findings to evaluate sex differences in the cellular and molecular mechanisms of HFpEF and aims to identify sex specific therapeutic targets for this disease.