Withers, Sarah - University of Salford - Biomedical Research Centre

个人简介

I am a Pharmacology graduate from the University of Sheffield where I received my honours degree in 2001. During my time there I met Dr Cathy Holt who worked in the Northern General Hospital and I carried out some summer research work which led to a PhD and a move to the University of Manchester. My PhD examined the role of apoptosis in restenosis in relation to c-Myb. I completed my PhD in 2005 and went on to work as a post-doctoral researcher in a collaborative position between Maternal and Foetal health and Cardiovascular Sciences at Manchester. The two year post examined the effects of internal and extravascular pressure on uterine arteries using a technique called pressure myography which takes segments of artery and allows physiological response to manipulation (pharmacological/physical) to be measured whilst maintained in a pressurised state. This project was to determine how arteries responded to contractions during pregnancy. I continued with my interest in cardiovascular physiology during a sustained post-doctoral position with Professor Heagerty at the Institute of Cardiovascular Sciences, University of Manchester. The overall focus of my 6 year position was to investigate the role of adipocytes in influencing vascular function using wire myography (vessels are mounted onto wires and their contraction measured via a transducer) and pharmacological techniques. I developed a personal interest in the inflammatory status of adipose tissue to understand the role of inflammation in dysregulating the function of perivascular adipose tissue and its effects on small artery function. Much of my work focuses on defining the relationship of inflammation with adipocytes and the pathways involved in the anticontractile effect of healthy adipose tissue and how these are affected in disease, such as obesity. My three main contributions to this area have been Development of an experimental model of hypoxia, recreating the perivascular environment in obesity Defining a key role for immune cells in mediating the loss of anticontractile capacity of perivascular adipose tissue Identifying key signalling pathways involved in mediating the adiponectin-dependent anticontractile effect of perivascular adipose tissue

研究领域

Obesity is increasing at an alarming rate and increases the risk of numerous conditions including cardiovascular disease and some cancers. There is a need to understand how this overweight state can alter function in order to identify new and effective therapies to treat obesity related disorders. My particular interest is the inflammatory status of adipose tissue, the immune cells involved and adipo- and cytokines produced and how this intricate and complex relationship becomes dysregulated when challenged by disease. I am especially interested in how vascular function is affected. I am experienced in a number of experimental methods summarised below, but I am highly skilled in using functional techniques to examine tissue reactivity, including wire and pressure myography. These techniques are useful as they facilitate the extrapolation of physiological responses to the in vivo situation by enabling interplay between cell types, which is difficult under in vitro culture conditions.

近期论文

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Agabiti-Rosei C, Withers SB, Belcaid L, De Ciuceis C, Rizzoni D & Heagerty AM. Blockade of the renin-angiotensin system in small arteries and anticontractile function of perivascular adipose tissue. Journal of Hypertension [In press] Heerkens EH, Quinn L, Withers SB, Heagerty AM. (2014) β Integrins Mediate FAK Y397 Autophosphorylation of Resistance Arteries during Eutrophic Inward Remodeling in Hypertension. J Vasc Res. 51(4):305-14 Agabiti-Rosei C, De Ciuceis C, Rossini C, Porteri E, Rodella LF, Withers SB, Heagerty AM, Favero G , Agabiti-Rosei E, Rizzoni D, Rezzani R. (2014) Anticontractile Activity of Perivascular Fat in Obese Mice and the Effect of Long-tern Treatment with Melatonin. Journal of Hypertension 32(6):1264-74. Withers SB, Simpson L, Fattah S, Werner ME. & Heagerty AM. (2014) cGMP dependent protein kinase (PKG) mediates the anticontractile capacity of perivascular adipose tissue. Cardiovasc Res. 1;101(1): 130-7 Withers SB, Passi N, Williams A, de Freitas D & Heagerty AM. (2013) Restoring the anticontractile properties of adipose tissue following hypoxia using erythropoietin. J Cardiovas Dis Res. 4(3):164-9 Withers SB, Taggart M & Austin CA. (2013) Isolated Small uterine arteries from non-pregnant and term pregnant rats exhibit regulatory responses to elevations in extravascular pressure. Placenta. 34(1):82-4 Malik N, Farrell K, Withers SB, Wright E & Holt CM (2013) A novel porcine model of early left ventricular dysfunction for translational research. Res Reports Clin Cardiol. 4:1-7