Andrew (AH) Baker
I have an established interested in basic and translational cardiovascular research. In particular, I have developed from inception a first-in-man clinical gene therapy study to prevent vascular remodelling in patients undergoing bypass graft surgery using an adenovirus overexpressing a matrix metalloproteinase inhibitor. We are currently making GMP grade virus and will conduct a phase I and II study, a project that is fully funded by the UK Medical Research Council. A second interest has been in the development of cell therapy approaches to promote vascular regeneration in patients with ischemic disease, both myocardial and peripheral. We have developed a GMP compliant system to produce a vascular endothelial cell product that shows high safety and efficacy in multiple animal models and is now being progressed to a first-in-man trial. At a more basic level, we have a deep interest in the regulation and function of non-coding RNA in vascular injury, repair and regeneration. Notably, we have studied a number of miRNA, in particular miR-21 and miR-143/5 in acute vascular injury, focusing on the importance in vein graft remodelling, in stent restenosis and small vessel remodelling associated with pulmonary hypertension. For example, we have shown that inhibition of miR-143 or miR-145 has a substantial therapeutic effect in remodelling. Recently, we have begun to dissect the expression patterns and function on long non-coding RNA in the vasculature. Using RNA sequencing technology and intervention studies, we have been documenting the importance of defined lncRNA in vascular smooth muscle cell proliferation, for example the lncRNA SMILR. We are now discovering the mechanism of action. In the endothelial compartment, we are interested in the effect of non-coding RNA in endothelial-to-mesenchyme transition and endothelial cell regeneration and have ongoing programmes using both in vitro studies and in vivo models of disease.