Dr. Victoria C Ridger BSc PhD

Lecturer

Address Department of Cardiovascular Science University of Sheffield Medical School Beech Hill Road Sheffield S10 2RX Tel: +44 (0)114 226 1410 Fax: +44 (0)114 271 1863 Email: v.c.ridger@sheffield.ac.uk

Biography:

I obtained an honours degree in Pharmacology from King´s College, London in 1994 during which time I spent a year in the lab of Professor W James Metzger in North Carolina. The project I undertook was investigating the inhibition of VLA-4 in asthmatic responses in a rabbit model and this, together with my PhD project carried out under the supervision of Professor Susan Brain, ignited my interest in inflammation.

My first postdoctoral position was at the NHLI, Imperial College, London in 1997 working with Professors Tim Williams and Ian Sabroe. I then moved to the Department of Cardiovascular Science at the University of Sheffield in 1998 to take up a Wellcome Trust funded postdoctoral position with Professor Paul Hellewell. This project involved establishing a mouse model of lung inflammation in order to investigate CD18-independent neutrophil trafficking.

In 2000 I started my third postdoctoral project with Dr Keith Norman and Professor Paul Hellewell investigating adhesion molecule interactions using microspheres in a mouse intravital microscopy model. I was awarded a BHF Intermediate Fellowship in 2002 and was then successful in gaining a New Blood Lectureship, which I started at the end of my Fellowship in 2005.

Research Interests:

My major research interests are in leukocyte trafficking and, in particular, mechanisms of adhesion and migration in the lung and cardiovascular system. Neutrophils are important cells involved in many inflammatory diseases but their involvement in atherosclerosis and atherogenesis remains unclear. Many of the factors shown to be important players in atherosclerosis are also known to be involved in regulating neutrophil recruitment to sites of injury.

During the course of my second postdoctoral position, I established a novel method for the isolation of pure populations of unactivated murine peripheral blood neutrophils. I carried out this work with a British Heart Foundation (BHF) funded PhD student whom I directly supervised. The use of these isolated cells has proved invaluable in investigating the role of these cells in inflammatory processes.

The award of my BHF Intermediate Fellowship allowed me to focus on direct investigation of the interaction of neutrophils and monocytes with the endothelium in large blood vessels where atherosclerosis predominantly occurs. At the same time my BHF funded PhD student investigated the role of NO in leukocyte-endothelial interactions using flow cytometry and an in vitro chemotaxis assay. During these investigations, we discovered that inhibiting the formation of NO through NOS inhibition with L-NAME resulted in the production of microparticles by neutrophils. These studies furthered my interest in the role of neutrophil-derived microparticles in augmenting the inflammatory response and, more specifically an interest in their potential role in atherosclerosis. I am particularly interested in elucidating the role of neutrophils in atherogenesis and, more specifically, neutrophil-derived microparticles on progression of atherosclerotic plaque formation and I have recently been awarded a BHF Project Grant to investigate these aspects of neutrophils function.

I currently have collaborations with Dr Helen Philippou and Dr Robert Ariens at the University of Leeds investigating in vivo thrombus formation in the femoral vein. I also have a long-standing collaboration with Professor Dan Cutler investigating the role of intracellular trafficking molecules in the modulation of leukocyte-endothelial interactions and leukocyte trafficking in vivo.

Teaching Interests:

Undergraduate: I am a non-clinical academic tutor for medical students.

Postgraduate: I routinely supervise Masters students from the Molecular Medicine MSc course and the Human Nutrition MMedSci course.

I am module leader for the Experimental Models of Vascular Disease module of the Cardiovascular Pathway on the Molecular Medicine MSc.

I am also deputy module leader for the Physiology module of the Human Nutrition MMedSci course.

I have been supervising PhD students since 1998 and have had 4 students successfully complete their PhD.

Professional Activities:

• Member of the UK Adhesion Society Committee.
• Treasurer for the Sheffield Regional Immunology group of the British Society for Immunology.
• Member of the UK Adhesion Society, British Society for Immunology and British Atherosclerosis Society.
• Reviewer for the MRC, BHF, Wellcome Trust, BJP, EJP.

Current Projects:

• Role of coagulation factor XIII in fibrin clot structure and thrombosis (2010-2013). MRC Project Grant. Dr R. Ariens, Dr H. Philippou and Dr V. Ridger.
• Regulation of monocyte-endothelial cell interactions by neutrophil-derived microparticles (2010-2012). British Heart Foundation Project Grant. Dr V. Ridger and Professor P. Hellewell.
• Regulation of factor XIIIa activity by plasmin: characterisation of proteolytic cleavage sites and functional influence on clot stabilisation (2009-2012). British Heart Foundation Project Grant. Dr H. Philippou, Dr V. Ridger, Dr. R. Pease and Professor P. Grant.
• Effects of nociceptin on the microcirculation during sepsis. (2008-2011). British Heart Foundation PhD Studentship. Professor P. Hellewell and Dr V. Ridger.
• The effects of anti-platelet therapies on neutrophil function. (2011-2014). PhD studentship funded by the Kingdom of Saudi Arabia. Dr V. Ridger, Professor R. Storey and Dr H. Judge.
• The effect of age on neutrophil-derived microparticle formation. (2012) MSc project. Dr V. Ridger and Dr A. Burnett.
• Neutrophil-derived microparticles contain NGAL and interact with human coronary artery endothelial cells. (2012) MMedSci Project. Dr V. Ridger and Dr A. Burnett.

Key Publications:

1. Doyle EL*, Ridger V*, Ferraro F, Turmaine M, Saftig P & Cutler DF. (2011) CD63 is an essential cofactor to leukocyte recruitment by endothelial P-selectin. Blood. 118: 4265-4273. *Joint first author.


2. Abbitt KB, Cotter MJ, Ridger VC, Crossman DC, Hellewell PG & Norman KE. (2009) Antibody ligation of murine Ly-6G induces neutropenia, blood flow cessation, and death via complement-dependent and independent mechanisms. J. Leukoc. Biol. 85: 55-63.


3. Ridger V, Krams R, Carpi A, Evans PC. Hemodynamic parameters regulating vascular inflammation and atherosclerosis: a brief update. (2008) Biomed. Pharmacother. 62: 536-40.


4. Nolan SL, Dixon R, Norman KE, Hellewell PG & Ridger VC. (2008) Nitric oxide regulates neutrophil migration through microparticle formation. Am. J. Pathol. 172: 265-273.


5. Ridger VC, Hellewell PG & Norman KE. (2005) L- and P-selectins collaborate to support leukocyte rolling in vivo when high affinity P-selectin-PSGL-1 interaction is inhibited. Am. J. Pathol. 166: 945-952.


6. Dockrell DH, Marriott HM, Prince LR, Ridger VC, Ince PG, Helewell PG & Whyte MK. (2003) Alveolar macrophage apoptosis contributes to pneumococcal clearance in a resolving model of pulmonary infection. J. Immunol. 171: 5380-5388.


7. Hicks AER, Nolan SL, Ridger VC, Hellewell PG & Norman KE. (2003) Recombinant P-selectin glycoprotein ligand-1 directly inhibits leukocyte rolling by all three selectins in vivo: complete inhibition of rolling is not required for anti-inflammatory effect. Blood. 101: 3249-3256.


8. Rowe SJ*, Allen L*, Ridger VC*, Hellewell PG & Whyte MKB. (2002) Caspase-1 deficient mice have delayed neutrophil apoptosis and a prolonged inflammatory response to lipopolysaccharide-induced acute lung injury. J. Immunol. 169: 6401-6407. (* Joint first author).


9. Cotter MJ, Norman KE, Hellewell PG & Ridger VC. (2001) A novel method for isolation of neutrophils from murine blood using negative immunomagnetic separation. Am. J. Pathol. 159: 473-481.

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