Warboys, Christina - Imperial College London - Department of Bioengineering

个人简介

Christina was awarded a British Heart Foundation Intermediate (Basic Science) Research Fellowship in 2016 to investigate the role of β-catenin in the regulation of mechanical signalling in the endothelium. Christina’s research interests are in the initiation and development of cardiovascular disease, in particular the cellular signalling mechanisms that define the spatial localisation of atherosclerosis. Christina obtained a first class honours degree in Medical Biochemistry from the University of Leicester before completing a PhD in Vascular Physiology in the Cardiovascular Division at King’s College London. In 2006 Christina began her postdoctoral research in the Department of Bioengineering at Imperial College London under the guidance of Professor Peter Weinberg investigating the effects of physiological chronic shear stress on endothelial cell permeability. In 2010 Christina moved to the National Heart and Lung Institute at Imperial College to work for Professor Paul Evans on a multi-disciplinary British Heart Foundation-funded project looking at the effects of flow and shear stress on endothelial apoptosis and senescence. In 2012 Christina returned to the to the Cardiovascular Division at King's College London to take up a research post with Professor Albert Ferro. This British Heart Foundation funded project identified a novel interaction between eNOS and β-catenin in endothelial cells and provided the first evidence for cross-talk between these two key regulatory pathways in vascular cells. Christina was recently awarded a BHF project grant along with Professor Ferro to supervise a postdoctoral researcher to continue these studies and determine the importance of this interaction in endothelial cell survival. During her postdoctoral studies Christina supervised several MRes, MSc and PhD students and has been actively involved in the day to day running of research facilities and numerous departmental and early career researcher committees. Christina has extensive teaching experience and before beginning her Research Fellowship worked as Teaching Fellow in Physiology within the Department of Bioscience Education at King’s College London.

研究领域

Atherosclerosis, the underlying cause of most cardiovascular disease, is associated with a number of risk factors e.g. age, hypertension and raised plasma cholesterol. Despite these systemically acting risk factors, atherosclerosis develops only at certain, predictable regions within arteries. The focal nature of atherosclerosis is widely attributed to variation in haemodynamic stresses acting on the vessel wall: lesions develop in areas of the vasculature exposed to low/oscillatory wall shear stress (the mechanical drag of blood on the vessel wall) whereas areas exposed to pulsatile flow with high wall shear stress are protected. Endothelial cells exposed to low/oscillatory wall shear stress exhibit chronic inflammatory activation, increased oxidative stress and increased rates of apoptosis, senescence and proliferation, which have all been linked to endothelial dysfunction and atherogenesis. Recent evidence suggests that multi-directional flow (transverse wall shear stress) is most strongly correlated with endothelial cell dysfunction and atherogenesis; these new insights highlight the need for better understanding of endothelial responses to flow direction. Christina’s programme of research will utilise an orbital shaker model to investigate endothelial cell responses to uniaxial and multidirectional flow direction in cultured cells. Christina is particularly interested in the role of β-catenin in mediating responses to flow. β-catenin serves multiple functions in endothelial cells as a component of the adherens junction and as a transcription factor where it acts as an effector of the Wnt signalling pathway. It has been linked to several putative mechanosensors and is activated in response to disturbed/multidirectional flow; it may therefore play a key role in regulating responses to mechanical stimuli, including flow direction. Christina’s research will focus on understanding the mechanical regulation of β-catenin and how this modulates endothelial cell function.

近期论文

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Passacquale G, Phinikaridou A, Warboys C, Cooper M, Lavin B, Alfieri A, Andia ME, Botnar RM, Ferro Aet al., 2015, Aspirin-induced histone acetylation in endothelial cells enhances synthesis of the secreted isoform of netrin-1 thus inhibiting monocyte vascular infiltration., Br J Pharmacol, Vol: 172, Pages: 3548-3564 Amini N, Boyle JJ, Moers B, Warboys CM, Malik TH, Zakkar M, Francis SE, Mason JC, Haskard DO, Evans PCet al., 2014, Requirement of JNK1 for endothelial cell injury in atherogenesis, ATHEROSCLEROSIS, Vol: 235, Pages: 613-618, ISSN: 0021-9150 Warboys CM, Chen N, Zhang Q, Shaifta Y, Vanderslott G, Passacquale G, Hu Y, Xu Q, Ward JP, Ferro Aet al., 2014, 25 Nitric Oxide-cGMP Signalling Promotes B-Catenin Nuclear Translocation and Transcriptional Activity in Endothelial Cells., Heart, Vol: 100 Suppl 1 Warboys CM, Chen N, Zhang Q, Shaifta Y, Vanderslott G, Passacquale G, Hu Y, Xu Q, Ward JP, Ferro Aet al., 2014, Bidirectional cross-regulation between the endothelial nitric oxide synthase and β-catenin signalling pathways., Cardiovasc Res, Vol: 104, Pages: 116-126 Warboys CM, de Luca A, Amini N, Luong L, Duckles H, Hsiao S, White A, Biswas S, Khamis R, Chong CK, Cheung W-M, Sherwin SJ, Bennett MR, Gil J, Mason JC, Haskard DO, Evans PCet al., 2014, Disturbed Flow Promotes Endothelial Senescence via a p53-Dependent Pathway, ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, Vol: 34, Pages: 985-995, ISSN: 1079-5642 De Luca A, Warboys C, Amini N, Ferreira P, Firmin D, Mason J, Sherwin S, Evans Pet al., 2013, TRANSCRIPTOME PROFILING IN PORCINE ARTERIES TO IDENTIFY NOVEL SHEAR-RESPONSIVE REGULATORS OF ENDOTHELIAL CELL FATE, Annual Conference of the British-Cardiovascular-Society (BCS), Publisher: BMJ PUBLISHING GROUP, ISSN: 1355-6037 Serbanovic-Canic J, de Luca A, Warboys C, Chico T, Evans Pet al., 2013, IDENTIFICATION OF NOVEL SHEAR STRESS-RESPONSIVE REGULATORS OF ENDOTHELIAL CELL DYSFUNCTION USING THE ZEBRAFISH MODEL, Annual Conference of the British-Cardiovascular-Society (BCS), Publisher: BMJ PUBLISHING GROUP, Pages: A6-A6, ISSN: 1355-6037 De Luca A, Warboys CM, Amini N, Ferreira P, Gatehouse P, Firmin D, Mason J, Sherwin S, Evans PCet al., 2012, IMAGE-BASED COMPUTATIONAL HEMODYNAMICS AND MICROARRAY ANALYSIS OF THE PORCINE AORTIC ARCH REVEALS A CORRELATION BETWEEN SHEAR STRESS AND ENDOTHELIAL CELL APOPTOSIS, PROCEEDINGS OF THE ASME SUMMER BIOENGINEERING CONFERENCE, PTS A AND B, Pages: 923-924 Warboys CM, Overby DR, Weinberg PD, 2012, Dendritic Cells Lower the Permeability of Endothelial Monolayers, CELLULAR AND MOLECULAR BIOENGINEERING, Vol: 5, Pages: 184-193, ISSN: 1865-5025 Warboys CM, de Luca A, Amini N, Evans PCet al., 2012, THE INFLUENCE OF FLOW ON VASCULAR ENDOTHELIAL CELL SENESCENCE, ATHEROSCLEROSIS, Vol: 225, Pages: E6-E6, ISSN: 0021-9150 Potter CMF, Lundberg MH, Harrington LS, Warboys CM, Warner TD, Berson RE, Moshkov AV, Gorelik J, Weinberg PD, Mitchell JAet al., 2011, Role of Shear Stress in Endothelial Cell Morphology and Expression of Cyclooxygenase Isoforms, ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, Vol: 31, Pages: 384-U314, ISSN: 1079-5642 Warboys CM, Amini N, de Luca A, Evans PCet al., 2011, When Stress Is Good, SCIENTIST, Vol: 25, Pages: 52-54, ISSN: 0890-3670 Warboys CM, Amini N, de Luca A, Evans PCet al., 2011, The role of blood flow in determining the sites of atherosclerotic plaques., F1000 Med Rep, Vol: 3 Warboys CM, Berson RE, Mann GE, Pearson JD, Weinberg PDet al., 2010, Acute and chronic exposure to shear stress have opposite effects on endothelial permeability to macromolecules, AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, Vol: 298, Pages: H1850-H1856, ISSN: 0363-6135 Warboys CM, Fraser PA, 2010, Hyperglycemia attenuates acute permeability response to advanced glycation end products in retinal microvasculature., Microvasc Res, Vol: 80, Pages: 174-176 Warboys CM, Toh HB, Fraser PA, 2009, Role of NADPH oxidase in retinal microvascular permeability increase by RAGE activation., Invest Ophthalmol Vis Sci, Vol: 50, Pages: 1319-1328