My research aims at providing new therapeutic options for patients with cardiac and peripheral ischaemia. In the era of “regeneration”, I am convinced that work on stem cells should progress together with investigations into the molecular causes of cardiovascular diseases. Hence, my programme focuses on both “causes” and “solutions”.
Research highlights include:
microRNAs as new therapeutic targets and biomarkers in ischaemic disease
microRNAs are non coding RNAs able to post-transcriptionally inhibit the expression of multiple target genes. For this reason, they can produce profound alteration in the molecular pathways regulating cardiovascular disease and “regeneration”. microRNAs have become extremely popular among biomedical scientists. My laboratory has developed early research in microRNAs regulating angiogenesis and endothelial behaviour in response to ischaemia and diabetes. We are member of a Leducq Transatlantic initiative for research and training in vascular microRNAs ( www.vascularmirnas.com) (officially starting in January 2014). Moreover, we are developing translational microRNAs work in the setting of cardiac surgery at the NIHR BRU in cardiovascular medicine in Bristol and the NIHR BRU at the Imperial College of London (in collaboration with Professor Gianni Angelini). My microRNA studies in critical limb ischaemia patients are currently developed through collaborations in Italy.
Nerve growth factor (NGF) therapy of ischaemic disease
NGF was the first growth factor to be identified and characterized, a breakthrough discovery for regenerative medicine that valued the Nobel prize to the Italian scientist Professor Rita Levi Montalcini in 1986. As its name suggests, NGF was for a long time studied in the context of neurobiology and neuromedicine. However, several years ago, I have discovered the proangiogenic activity and therapeutic potential of NGF, focussing at that time on limb ischaemia. The British Heart Foundation (BHF) has sponsored my research on the cardiac applications of NGF, first with a Basic Science Lectureship and now with my Senior Research Fellowship. We have so far showed that local NGF gene therapy is able to promote reperfusion, protect cardiomyocytes from death and increase the abundance of stem cells in the infarcted heart (using a mouse model of research) and that it improves post-infarct cardiac function and survival rate. Moreover, NGF gene therapy protects the diabetic heart and kidneys in mice. We have now started a pathway to translate NGF to a first in man trial in patients with coronary artery disease leading to myocardial ischaemia.
Stem cells are the holy grail of both medical scientists and lay persons. Several kinds of stem cells have been proposed for cardiovascular therapies. My laboratory focuses at the most powerful of them, the embryonic stem cells (ESCs). We are improving the process of derivation of vascular progenitor cells from ESCs and trying to better understand their paracrine regenerative properties. Moreover, in collaboration with the Universities of Glasgow and Edinburgh and with the Roslin cells ltd we are developing a pathway to translate clinical grade human ESCs-derived vascular progenitor to a trial in patients with critical limb ischaemia. This would be the very first trial base d on ESCs in cardiovascular patients and we are particularly excited. The main collaborator for this work is Professor Andrew Baker.
Finally, I am contributing to the molecular characterization of a new adult stem cell population (the “Bristol pericytes”), which Professors Paolo Madeddu and Gianni Angelini have discovered to be present in vena saphena leftover from coronary-artery-by-pass-graft (CABG). This long-term project should soon been translated in a phase 1 clinical trial in angina patients (as part of the NIHR-BRI in cardiovascular medicine in Bristol).