Research Summary
For over 25 years, my research group has been researching in the area of neural control of cardiac excitability. Arrhythmia is often associated with autonomic imbalance and normally precedes sudden cardiac death. However, we still do not fully understand how the two branches of the cardiac autonomic nervous system and their local circuits communicate, and whether their uncoupling is central to the onset of ventricular and atrial arrhythmia. We collaborate with world-leading groups in the USA and NZ as we build a state-of-the-art integrated anatomical and physiological framework that will facilitate guided therapies. At Oxford we have shown how intracellular molecules (cyclic nucleotides) coupled to neuropeptides and the endogenous gas nitric oxide act as key intermediaries in regulating abnormal neurotransmission in cardiovascular disease. We employ an integrated approach: by studying the molecular and electrical properties of cardiac tissue in-vitro and in-vivo using gene transfer, western/northern blotting techniques, fluorescence, including FRET, electrophysiological recordings (single cell to multi-electrode array mapping) and network models to reconstruct (using parallel computing) biophysical events. More recently we have used bulk and single cell RNAseq to facilitate target discovery in human iPSC neuronal and myocyte co-cultures from patients with cardiac channelopathies to test the idea that the disease also resides in the nervous system. We encourage our research students to use a multidisciplinary approach in order to facilitate the integration of their results back into whole systems.