Dr Jillian Simon
Oxford BHF CRE Basic Science Intermediate Transition Fellow
- Start Date: 01/02/2022
- End Date: 31/01/2024
- BHF CRE Mentor: Prof Barbara Casadei
Research Project Title: Nutrient sensing and lysosomal regulation by oxidized PKARIα
My research aims to unravel the key signalling pathways supporting myocardial adaptation during nutrient deficiency, and examine the extent to which down-regulation of these pathways in metabolic disease settings might contribute to overall cardiac pathology. My BHF CRE Transition Fellowship is focused specifically on nutrient sensing and signalling in the heart by PKA-RIα (or type-1 PKA), which we’ve discovered plays a vital role in the promoting the myocardial adaptive response to nutrient depletion, via it’s interaction with the lysosome. Using a multifaceted approach (e.g., biochemistry, molecular biology, proteomics and genetically-altered mouse models), we hope to gain a better understanding of how limited nutrient availability is communicated to PKARIα, and what effect this communication imposes on lysosomal function, adaptation and cell survival. In the longer term, I aim to take this work forward as part of an external funding application investigating how pathogenic alterations in this signalling cascade influences cardiovascular disease development.
In organs like the heart, where there is little regenerative capacity, it is imperative that adaptive mechanisms are in place to combat metabolic stress and ensure cell survival when nutrient levels become depleted. Governing these adaptive processes are energy-sensitive signalling mediators, which rapidly sense changes in external nutrient status and activate pro-survival responses that help maintain homeostasis. Because of these adaptive responses, the heart not only copes with brief periods of nutrient deficiency – such as intermittent fasting – but it can also experiences additional cardiovascular benefits as a result of such dietary interventions. Opposingly, in disease settings such as obesity and type-2 diabetes, persistent nutrient over-abundance can lead to suppression of these cardioprotective signalling cascades, resulting in maladaptive remodelling and poorer prognostic outcomes following adverse cardiac events.
2002-2006 BSc Exercise and Health Science, Alma College (Alma, MI. USA)
2007-2013 American Heart Association Pre-doctoral Fellow, Department of Physiology and Biophysics, University of Illinois at Chicago (Chicago, IL. USA)