Professor Sheila Francis BSc PhD
Professor of Cardiovascular Biology
Department of Infection, Immunity & Cardiovascular Disease
University of Sheffield
Beech Hill Road
Tel: +44 (0)114 215 9501
Fax: +44 (0)114 271 1863
I joined the University of Sheffield in 1990 after a BBSRC CASE PhD studentship at the University of Manchester. After 4 years as a Postdoctoral Research Associate in Cardiac Surgery (with Angelini) and Molecular Medicine (with Duff), I held an Independent Open Competition Fellowship from the Lloyd´s Tercentenary Foundation on the molecular and inflammatory basis of coronary artery disease. After being appointed Lecturer in 1994, I spent a sabbatical period in the Hynes Lab at MIT as a Fulbright Scholar. I am currently Professor of Cardiovascular Biology at the University of Sheffield.
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 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 acute presentation of atherosclerosis after chronic infection. These studies are being undertaken in collaboration with colleagues in the Departments of Cardiovascular Science, Infection and Immunity and Chemistry at the University of Sheffield, the Universities of Manchester (Pinteaux, Allan, Rothwell), Leicester (Stover), the University of Virginia (Owens, Abbate) and others.
I teach on the MSc in Molecular Medicine and on the new MRes in Cardiovascular Medicine – From Molecules to Man. I also teach on phase 2a (Cardiology) MBChB. I co-lead (with Professor Nigel Wheeldon) an undergraduate BMS 3rd year module ‘Cardiovascular Pharmacology – personalising medicine’.
- Translational Research Projects Panel Member, Heart Research UK (HRUK) current.
- Training Awards Committee (TAC), BBSRC (2006-2010).
- Project Grants Committee, British Heart Foundation (2007-2010).
- Secretary of the British Atherosclerosis Society (September 2018 - )
- Release of IL-1 from endothelial cells (Embassy of Libya).
- Tribbles and Atherosclerosis (EU ITN, BHF (with Kiss-Toth)).
- S.pneumoniae infection and atherosclerosis (MRC (with Dockrell)).
- Carbon monoxide releasing molecules (BHF (with Gunn/Iqbal, Motterlini and Mann)).
- TILRR in inflammation and vascular disease (BHF (with Qwarnstrom)).
- Hypoglycaemia and risk of atherosclerosis (MRC (with Sabroe and Heller)).
- Interleukin-1 alpha versus interleukin-1 beta in atherosclerosis and hypertension? (BHF (with Pinteaux and Ashton, Manchester)).
- Neurovascular funtcion in atherosclerosis (with Berwick, NICAD).
For key publications see below. For a full list of publications click here.
- Gomez D, Baylis RA, Durgin BG, Newman AAC, Alencar GF, Mahan S, St. Hilaire C, Müller W, Waisman A, Francis SE, Pinteaux E, Randolph GJ, Gram H & Owens GK (2018) Interleukin-1β has atheroprotective effects in advanced atherosclerotic lesions of mice. Nature Medicine, 24(9), 1418-1429. View this article in WRRO
- Alfaidi MA, Chamberlain J, Rothman A, Crossman D, Villa‐Uriol MC, Hadoke P, Wu J, Schenkel T, Evans PC & Francis SE (2018) Dietary Docosahexaenoic Acid Reduces Oscillatory Wall Shear Stress, Atherosclerosis, and Hypertension, Most Likely Mediated via an IL‐1–Mediated Mechanism. Journal of the American Heart Association, 7(13). View this article in WRRO
- Pickworth JA, Rothman A, Iremonger J, Casbolt H, Hopkinson K, Hickey P, Gladson S, Shay S, Morrell N, Francis S, West JD & Lawrie A (2017) Differential IL-1 signaling induced by BMPR2 deficiency drives pulmonary vascular remodeling. Pulmonary Circulation. View this article in WRRO
- Smith SA, Samokhin AO, Alfadi M, Murphy EC, Rhodes D, Kiss-Toth E, Storey RF, Yee S-P, Francis SE & Qwarnstrom EE (2017) The IL-1RI Co-Receptor TILRR (FREM1 Isoform 2) Controls Aberrant Inflammatory Responses and Development of Vascular Disease. JACC - Journal of the American College of Cardiology bts, 2(4), 398-414. View this article in WRRO
- Holen I, Lefley DV, Francis SE, Rennicks S, Bradbury S, Coleman RE & Ottewell P (2016) IL-1 drives breast cancer growth and bone metastasis in vivo.. Oncotarget, 7, 75571-75584. View this article in WRRO
- Mahmoud M, Kim HR, Xing R, Hsiao S, Mammmoto A, Chen J, Serbanovic-Canic J, Feng S, Bowden NP, Maguire R, Ariaans M, Francis S, Weinberg PD, Van der Heiden K, Jones EA, Chico TJ, Ridger VC & Evans PC (2016) TWIST1 Integrates Endothelial Responses to Flow in Vascular Dysfunction and Atherosclerosis. Circulation Research, 119, 450-462. View this article in WRRO
- Rothman AM, Arnold N, Pickworth J, Iremonger J, Ciuclan L, Allan R, Guth-Gundel S, Southwood M, Morrell N, Thomas M, Francis S, Rowlands D & Lawrie A (2016) MicroRNA-140-5p and SMURF1 regulate pulmonary arterial hypertension. Journal of Clinical Investigation, 126(7), 2495-2508. View this article in WRRO
- Alfaidi M, Wilson H, Daigneault M, Burnett A, Ridger V, Chamberlain J & Francis SE (2015) Neutrophil Elastase promotes Interleukin-1β secretion from Human Coronary Endothelium. Journal of Biological Chemistry, 290, 24067-24078. View this article in WRRO
- Dénes Á, Pradillo JM, Drake C, Sharp A, Warn P, Murray KN, Rohit B, Dockrell DH, Chamberlain J, Casbolt H, Francis S, Martinecz B, Nieswandt B, Rothwell NJ & Allan SM (2014) Streptococcus pneumoniae worsens cerebral ischemia via interleukin 1 and platelet glycoprotein Ibα. Annals of Neurology, 75(5), 670-683. View this article in WRRO
- West LE, Steiner T, Judge HM, Francis SE & Storey RF (2014) Vessel wall, not platelet, P2Y12 potentiates early atherogenesis.. Cardiovasc Res, 102(3), 429-435.
- Bazaz R, Marriott HM, Francis SE & Dockrell DH (2013) Mechanistic links between acute respiratory tract infections and acute coronary syndromes.. J Infect, 66(1), 1-17.
- Hameed AG, Arnold ND, Chamberlain J, Pickworth JA, Paiva C, Dawson S, Cross S, Long L, Zhao L, Morrell NW, Crossman DC, Newman CMH, Kiely DG, Francis SE & Lawrie A (2012) Inhibition of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) reverses experimental pulmonary hypertension.. J Exp Med, 209(11), 1919-1935. View this article in WRRO
- Denes A, Drake C, Stordy J, Chamberlain J, McColl BW, Gram H, Crossman D, Francis S, Allan SM & Rothwell NJ (2012) Interleukin-1 Mediates Neuroinflammatory Changes Associated With Diet-Induced Atherosclerosis. Journal of the American Heart Association, 1(3). View this article in WRRO