Targeting altered cardiac glucose metabolism in the cardiac complications of diabetes

Research Opportunity
PhD students, Master of Biomedical Science
Number of Master Places Available
1
Primary Supervisor Email Number Webpage
Dr lea Delbridge lmd@unimelb.edu.au
Co-supervisor Email Number Webpage
Prof Rebecca Ritchie

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).

Project Details

The increasing global prevalence of type 2 diabetes (T2D) and our aging population has given rise to an epidemic of heart failure (HF). Up to one-third of patients in clinical HF trials are diabetic, and diabetes is an independent predictor of poor outcome. Despite the higher rate of HF in these patients, no specific treatment for HF exists for T2D patients. We have identified novel mechanisms for limiting T2D-associated cardiomyopathy that could pave the way for the development of much needed, novel therapies that are specific for diabetic HF. Increased glucose flux through the hexosamine biosynthesis pathway (HBP) has now emerged as a key mediator of the adverse effects
of diabetes on the heart. As a result of this HBP overdrive, increased cardiac levels of the glucose metabolite called O-GlcNAc increases susceptibility of a range of proteins to O-GlcNAc modification, altering their function. We propose that this route of glucose metabolism impairs left ventricular (LV) function, and will focus in particular on O-GlcNAcylation of key components within the cardiomyocyte. The aim of this project is to demonstrate that cardiac‐directed therapeutic targeting of this ROS-hexosamine biosynthesis axis delays or even overcomes diabetes‐induced
cardiac dysfunction in the intact heart in vivo, and to investigate susceptibility of specific components within the cardiomyocyte to O-GlcNAcylation, and how this impacts on diabetes induced HF.



Research Opportunities

PhD students, Master of Biomedical Science
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.


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