Supervisors: Prof Neil Herring & Prof David Paterson (DPAG)
“ The autonomic control of ventricular arrhythmias”
Both the rate and force of contraction of the heart are influenced by the autonomic nervous system. This is essential for exercise and carrying out the activities of daily life. However, when the heart electrical or structural abnormalities, particularly following a “heart attack” (or myocardial infarction), stimulation by the group of nerves that speed up cardiac contraction can lead to dangerous heart rhythms and sudden cardiac death. Nerves that slow down cardiac contraction are able to protect against this. The balance between these two groups of nerves is therefore critical for long-term survival in many cardiovascular diseases.
The textbook view of how these nerves work is that they merely respond to reflexes mediated through the brain. However, we have found that the system is not "hard wired" and its behaviour can be greatly influenced by local chemical modulators both within the neurons (such as nitric oxide), and from neighbouring neurons (such as neuropeptide Y and galanin), as well as nearby blood vessels (such as CNP and angiotensin II) and the injured heart itself (BNP). During my DPhil, I aim to study how these local neuromodulators influence these nerves in order to develop therapeutic strategies for treating cardiovascular disease, the number one cause of death in the western world. My project will pay particular attention to neuropeptide-Y and how it influences both heart rhythm and the blood supply to the heart itself.
The Herring and Paterson groups use a variety of experimental techniques on the molecular (qPCR, Western blotting, IHC, ELISA assays and viral vector delivery of genes and RNAi), and cellular level (fluorescence and FRET imaging, neurotransmitters release measurements) all the way through to organ behaviour in-vitro (Langendorff perfused hearts) and in-vivo (through haemodynamic measurements).
I graduated from Imperial College London in 2014, obtaining BSc (Hons) in Pharmacology and Translational Medical Science. During my degree I worked in the Department of Neuroscience studying the role of iron chelators in Alzheimer's disease. I spent a year of my degree in industry at GlaxoSmithKline, working in the quantitative pharmacology division - department of immuno-inflammation.
I earned my MSc in Pharmacology at the University of Oxford, completing a project with Dr Neil Herring (DPAG), focusing on the autonomic control of ventricular arrhythmias. This is the work I am continuing during my DPhil.
The Role of Neuropeptide Y in Cardiovascular Health and Disease
- PDF - Frontiers Review
- PDF document 1.4 MB
Neuropeptide Y (NPY) is an abundant sympathetic co-transmitter, widely found in the central and peripheral nervous systems and with diverse roles in multiple physiological processes. In the cardiovascular system it is found in neurons supplying the vasculature, cardiomyocytes and endocardium, and is involved in physiological processes including vasoconstriction, cardiac remodeling, and angiogenesis. It is increasingly also implicated in cardiovascular disease pathogenesis, including hypertension, atherosclerosis, ischemia/infarction, arrhythmia, and heart failure. This review will focus on the physiological and pathogenic role of NPY in the cardiovascular system. After summarizing the NPY receptors which predominantly mediate cardiovascular actions, along with their signaling pathways, individual disease processes will be considered. A thorough understanding of these roles may allow therapeutic targeting of NPY and its receptors.