Cardiovascular Proteomics

Lab head: Dr Melanie White
Location: Level 4 East, The Hub, Charles Perkins Centre, Building D17

Laboratory Interests: Understanding cardiac comorbidities of type 2 diabetes.

Lab members: 2 PhD students
Funding: ARC, NHMRC and Ramaciotti Foundation
Research approach equipment: We use rat models of disease, Langendorff perfusion of isolated hearts, proteomics, mass spectrometry, western blotting, and agonist/antagonist therapeutics in our research.

Cordwell, SJ, Edwards, AVG, Liddy, KA, Moshkanbaryans, L, Solis, N, Parker, BL, Yong, ASC, Wong, C, Kritharides, L, Hambly, BD and White, MY. (2012) Release of Tissue-specific Proteins into Coronary Perfusate as a Model for Biomarker Discovery in Myocardial Ischemia/Reperfusion Injury. Journal of Proteome Research 11, 2114-2126.

Edwards, AVG, Cordwell, SJ and White, MY. (2011). Phosphoproteomic Profiling of the Myocyte. Circulation-Cardiovascular Genetics 4. DOI: 10.1161/CIRCGENETICS.110.957787

Why do diabetic hearts behave differently from normal hearts?

Primary supervisor: Melanie White

With an increasing prevalence of obesity, lifestyle-induced Type 2 Diabetes (T2DM) is becoming increasingly common. T2DM accounts for approximately 90% of all diabetic patients and has a 68% mortality rate associated with cardiovascular disease. By comparison with non-diabetic cohorts, there is a 4-fold increase in the risk of developing cardiovascular disease and a 6-fold increase in mortality after myocardial infarction. We want to understand at the molecular level, why diabetic hearts respond so poorly to myocardial challenges including ischemia.

In the past, we have investigated the protein profile of normal hearts under varying conditions (including ischemia/reperfusion). Changes in abundance and modification status are routinely observed across numerous proteins, with some proteins released from the cell and detected as biomarkers. For this project we aim to investigate how T2DM impacts myocardial proteins in similar conditions.

We have access to a model of T2DM, where hyperglycemia is evident, but insulin therapies are not required. We use our langendorff perfusion system to investigate the functional response of these T2DM tissues to myocardial challenges. At the completion of these protocols, we extract the myocardial proteins and determine those that are modified by comparison with normal hearts. To achieve this we use gel-based (1-dimensional and 2-dimensional gel electrophoresis) and gel-free (liquid chromatography) techniques to separate proteins, facilitating visualisation of proteins and peptides modified in the T2DM hearts. We identify and characterise those changed proteins by mass spectrometry, whereby peptides are identified by both their mass and sequence.

Discipline: Pathology
Co-supervisors: Stephen Twigg, Stuart Cordwell