a) Coronary Microvascular Dysfunction (CMD) is a common but under-recognised condition that disproportionately affects women, often missed using conventional diagnostic tests and lacking mechanistic therapies. This project aims to understand how disordered energy use in the heart contributes to CMD, and whether this can be corrected using novel personalised treatments guided by advanced imaging and patient-derived cellular models. This will build upon the MRC-funded studies such as ChaMP-CMD (led by King’s College London and PRIZE (led by University of Glasgow) both published in Circulation in 2024, deriving mechanistically targeted therapies for CMD.
(b) The student will explore how the heart’s fuel preference, between fats and glucose, may underlie different CMD subtypes. Gold standard invasive assessments will be used to characterise patients in the cardiac catheterisation laboratory and state-of-the-art non-invasive techniques including perfusion cardiac MRI and phosphorus magnetic resonance spectroscopy (³¹P-MRS), used to assess whether shifting energy usage improves the resilience of the heart to ischaemia. In parallel, they will harness innovative blood vessel organoid (BVO)s to create ex-vivo models of the microcirculation, derived from invasively characterised patient’s peripheral blood mononuclear cells, to investigate dysfunctional cellular biology and test personalised therapies. The student will receive training in cardiac imaging, in vivo physiology, clinical trial methodology and application, cellular and molecular biology, and advanced data analysis. The project is well-suited to students interested in translational cardiovascular research with strong clinical relevance.
(c) Project Aims:
• Understand the metabolic drivers of distinct CMD endotypes, using invasive physiology, novel imaging tools and cellular biology
• Test targeted therapies for CMD subtypes
(d) PhD Objectives:
• Year 1: Training in cardiac MRI, invasive physiology and organoid generation; rotation project (see below); attend clinics, begin recruitment and sample collection
• Year 2: Assess therapeutic response to SGLT2 inhibitors using imaging and begin organoid-based screening
• Year 3: Build ³¹P-MRS experience at KCL in collaboration with Cambridge University, identify new therapy targets
• Year 4: Integrate datasets, validate biomarkers, write thesis, and publish findings
(e) 3-Month Rotation Project (for MRes + PhD Pathway):
Develop and validate blood vessel organoids from healthy donors and characterise their metabolic responses to glucose and fatty acid manipulation using ³¹P-MRS