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Professor Sarah George

Professor Sarah George

Professor Sarah George
B.Sc., Ph.D.(Wales)

Professor of Cardiovascular Signalling

Area of research

Cardiovascular Signalling

Office Room 144
Level 7,
Bristol Royal Infirmary, Upper Maudlin Street BS2 8HW
(See a map)

+44 (0) 117 34 23154

Summary

Coronary artery bypass surgery is a popular surgical technique used to treat patients with heart disease. The first coronary artery bypass was performed in 1960, but despite enhanced surgical techniques over the last 50 years, this surgery technique still requires improvement as the grafts themselves become diseased. Our research looks into the mechanisms underlying the failure of bypass grafts, by studying the behaviour of the smooth muscle cells in the graft.

We are currently examining a relatively unstudied area; the role of cell-cell contacts via cadherins in the regulation of smooth muscle cell behaviour and cardiovascular disease.

Our studies have demonstrated that this is a very interesting and multi-faceted area. We have observed that N-cadherin regulates smooth muscle cell behaviour including cell proliferation, migration and survival. We have also observed that this is due in part by initiating transcription of specific genes involved in smooth muscle cell behaviour via ß-catenin.

We have also become interested in a family of proteins called WNTs. These proteins were first identified in flies but the evidence for a vital role in human disease is gaining momentum. Together this research has helped us to propose novel regulators of graft failure which may help us find a cure for bypass graft disease.

Biography

Born in Bristol, Sarah Jane George graduated in Applied Biology from University of Wales in Cardiff in 1991. Following a PhD with Professor Andrew Newby at the University of Wales College of Medicine in Cardiff - entitled ‘Growth Factors and Smooth Muscle Cell Proliferation@ - she moved to the University of Bristol to carry out postdoctoral studies with Professor Gianni Angelini.  At this stage her studies centred on matrix degrading metalloproteinases and their inhibitors tissue inhibitors of metalloproteinases (TIMPs) particularly in the context of vein graft failure.

In the last 10 years she has undertaken a new area of research, the role of cell-cell contacts and Wnt signalling in the regulation of smooth muscle cell behaviour and their involvement in restenosis and atherosclerotic plaque stability.

Her contribution to this new area of research was recognised by the British Atherosclerosis Society by the award of the ‘2005 John French Lecture’ at the British Atherosclerosis Society (BAS) Meeting in Oxford.

Professor George has published more than 60 research papers, reviews and book chapters and a recent book entitled 'Atherosclerosis: Molecular and Cellular Mechanisms'. Recently, she edited a book with Dr Johnson entitled 'Atherosclerosis: Molecular and Cellular Mechanisms' for Wioley-Blackwell. She has also obtained research grants to support her research and establish an independent research group. As a peer-nominated committee member of the British Society for Cardiovascular Research (BSCR) and currently the British Atherosclerosis Society Secretary she has also contributed to the organisation of scientific meetings in the United Kingdom.

Keywords

  • Cell-cell adhesion
  • Smooth muscle cells
  • WNTs
  • Graft failure
  • Cadherins
  • Proliferation
  • Migration
  • Apoptosis
  • Plaque rupture

Expertise

We are currently examining a relatively unstudied area; the role of cadherin mediated cell-cell contacts and Wnts in the regulation of smooth muscle cell behaviour and cardiovascular disease including restenosis and atherosclerosis. Our studies have demonstrated that this is a very interesting and multi-faceted area. We have observed that N-cadherin regulates smooth muscle cell behaviour including cell proliferation via increasing beta-catenin signalling and modulation of cyclin D1 and p21. We have also identified that N-cadherin is cleaved during smooth muscle cell proliferation by matrix degrading metalloproteinases (MMP-9 and MMP-12). Studies are underway to determine the involvement of Wnt proteins in VSMC proliferation, migration and survival. Additionally we have shown that N-cadherin is an important pro-survival signal for smooth muscle cells and a soluble mimetic of N-cadherin reduces smooth muscle cell apoptosis and reduces features of plaque rupture.

  • cells
  • cadherins
  • smooth muscle cells
  • cardiovascular disease
  • proliferation
  • migration
  • apoptosis
  • Memberships

    Organisations

    Bristol Medical School (THS)

    Other sites

    Academic staff

    Recent publications

    View complete publications list in the University of Bristol publications system

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