Professor Sheila Francis

I have a long-standing interest in the role of interleukin-1 (IL-1) and its naturally occurring antagonist, IL-1ra in modulating vascular cell function in experimental models and in human disease. Over the past 10-15 years, I have shown that IL-1 and IL-1ra are increased in diseased human arteries and in other experimental cardiovascular systems. I described the association of a genetic variant of IL-1ra with coronary artery disease and showed that this variant alters protein levels and the biology of endothelial cells.

Programme funding from the British Heart Foundation (with Professor David Crossman) allowed the use of strategies to inhibit IL-1 in several experimental models including atherosclerosis in mice. The impact of this early work alongside that of others has now been translated to man through the ILA-HEART and CANTOS trials.

My current research areas of interest relate to the mechanisms by which IL-1 is released from vascular cells especially endothelial cells, IL-1 related molecules and their antagonists, and the role of IL-1 in complex vascular phenotypes such as inflammatory vascular plaques in the brain and the mixed models of atherosclerosis after chronic infection and also episodes of hypoglycaemia. More recently, I have become interested in the control of endothelial senescence and impacts upon age-related diseases working with colleague in HELSI.

I collaborate with colleagues in Infection, Immunity and Cardiovascular Disease, Metabolism, Psychology and Neuroscience at the University of Sheffield and with colleagues at the Universities of Manchester (Pinteaux, Allan), the University of Virginia (Owens, Abbate) and others.

Current projects

1. Release of IL-1 from vascular cells especially endothelial cells.
2. S.pneumoniae infection and atherosclerosis (with Bazaz and Dockrell (Edinburgh)).
3. Hypoglycaemia and risk of atherosclerosis (with Iqbal and Heller).
4. Interleukin-1 alpha versus interleukin-1 beta in atherosclerosis, hypertension and stroke (with Pinteaux and Allan, Manchester)).
5. Macrophage phenotypes in human carotid atherosclerosis (with Kiss-Toth and Redgrave).
6. Neurovascular function in atherosclerosis (with Wharton, Berwick and Howarth).
7. Approaches to alter endothelial senescence and ageing (with Bellantuono).
8. PKC alpha/TGF beta axis in atherosclerosis and medical calcification (with Brennan, Canfield and Borland, Manchester)
9. Vascular Brain pathology (with Simpson and Wharton)
10. Inflammation, atherosclerosis and molecular manipulation of the microbiome (with Jon Shaw)