Associate ProfessorMelanie White

The leading cause of death among people with type 2 diabetes (T2D) is cardiovascular disease, with a 4x higher risk of heart attack and poorer outcomes following a single cardiac event, both major factors contributing to this outcome. Numerous promising strategies to protect patients against the devastating effects of a heart attack failed to progress to the clinic because they offer no benefit to patients with type 2 diabetes. There is a suggestion that the heart is 'primed' by the changing metabolic environment with T2D (cardiometabolic syndrome and diabetic cardiomyopathy) before a heart attack, resulting in this reduced functional recovery.

Melanie's group has developed preclinical models of diabetic cardiomyopathy to delineate the distinct contributions of energetic excess and pancreatic insufficiency on the cardiac molecular environment and, ultimately, to contractile performance and recovery. Isolated ex vivo cardiac perfusion is instrumental to their research, enabling investigation of myocardial contractile performance under tightly regulated conditions. Furthermore, Langendorff perfusion allows her group to perform pharmacological studies, testing the impact of direct infusion of kinase inhibitors, redox scavengers, and diverse energy sources on cardiac performance. Her work in this area has seen her collaborate with ADInstruments and highlighted by webinars and "ask the experts" videos for Inside Scientific.

Melanie's group uses high-resolution mass spectrometry to perform multi-omics analyses, investigating changes in proteins, lipids, metabolites, and small molecules. These are critical molecular mediators that enable cells to adapt to changes in the local environment, ultimately controlling the response to disease (disease phenotype). Melanie's group is also interested in the final regulatory mechanism in the disease phenotype, post-translational modifications, which can influence protein structure, function, and localisation. The dynamic nature of such PTMs can alter the disease phenotype within seconds, including redox modifications and phosphorylation. Using high-resolution mass spectrometry has allowed Melanie's group to delve deeply into the disease phenotype and identify targets for validation studies. Her expertise in this area has led to numerous successful collaborations and follow-up studies in clinical cohorts.