Dr Pavlovic’s research is focused on three major themes:
- Regulation of the cardiac sodium pump
As the only quantitatively significant sodium efflux pathway out of cardiac cells, sodium pump is the primary regulator of intracellular sodium. The trans-membrane sodium gradient it establishes is essential for normal electrical excitability, numerous coupled-transport processes and, as the driving force for Na/Ca exchange, thus setting cardiac calcium load and contractility. As sodium influx varies with electrical excitation, heart rate and pathology, the dynamic regulation of sodium efflux is essential. Phospholemman, a 72 amino acid accessory protein that forms part of the sodium pump complex, is the key nexus linking cellular signaling to pump regulation. Phospholemman is the target of a variety of kinase and phosphatase-mediated post-translational modifications and these can dynamically alter the activity of the sodium pump. Current research is focused on identifying novel phosphatase-mediated regulatory pathways for the cardiac sodium pump and how these regulatory pathways are modified in disease.
- The role of Cardiotonic Steroids in the heart
Cardiotonic steroids are a new class of hormones that circulate in the blood and have the ability to bind and inhibit the sodium pump, thus regulating intracellular sodium in every living cell. During states of chronic volume expansion, such as chronic kidney disease or heart failure, cardiotonic steroids are elevated in the blood and have been implicated in development of cardiovascular disease. Current research is directed towards understanding the relationship between endogenous cardiotonic steroid concentrations in chronic kidney disease patients and development of cardiac dysfunction.
- Causes of Atrial Fibrillation
Atrial fibrillation is the most common sustained arrhythmia. Electrical and structural remodelling of the myocardium are the two main causes of atrial fibrillation development. Atrial fibrillation is mainly a left atrial disease and Pitx2c has been identified as the single most enriched gene in the left atrium, suggesting a relevant role of this gene for left atrial function in health and disease. Current research is focused on identifying whether Pitx2c is involved in the pathophysiology of atrial fibrillation.
Started Sep 2015 – “Regulation of intracellular sodium in the atria”
Started Sep 2016 – “Translating the effect of rate control therapy in atrial fibrillation: from cellular response to cardiac function”
Started Sep 2016 – “Developing a high-resolution optical mapping setup with integrated high-throughput analysis capabilites for dissecting molecular mechanisms of cardiac arrhythmias”
Started Feb 2017 – “Cardiac estrogen synthesis and arrhythmia