infection and inflammation
Name: Dr Sandra Sacre
Academic position: Lecturer of molecular cell biology,
Honorary Lecturer at Imperial College London
Research: Regulation of inflammatory cell signalling pathways
Contact details:
Trafford Centre
Brighton and Sussex Medical School
University of Sussex
Falmer
Brighton
East Sussex
BN1 9RYTel: +44 (0) 1273 872865
Fax: +44 (0) 1273
E-mail:
Biography:
- 1996 BSc (Physiology), University College London
- 2000 PhD (Physiology), University College London
- 2000 Research Associate, Medicine, Royal Free Hospital, University College London
- 2002 Research Fellow, The Kennedy Institute of Rheumatology Division, Imperial College London
Research focus: macrophage biology, innate immunity, toll-like receptor signalling, regulation of inflammation, mechanisms of autoimmune disease pathogenesis, rheumatoid arthritisCurrent research.
Current research:
My research goal is to gain a more comprehensive understanding of how innate immune receptors are activated and regulated in chronic inflammatory conditions and to identify which receptors and signalling pathways contribute towards disease pathogenesis. My work focuses on autoimmune diseases and has a particular focus on rheumatoid arthritis, a chronic and debilitating disease that affects 1% of the world’s population.
Toll-like receptors (TLR), a family of innate immune receptors that are evolutionary conserved and form an important part of the immune recognition of pathogens, are suggested to contribute to rheumatoid arthritis disease pathogenesis. I have identified a role for TLR signalling in the production of pro-inflammatory factors from rheumatoid tissue and identified TLR8 as a significant contributor in this process. Elucidating the mechanisms that perpetuate inflammation in rheumatoid arthritis is essential if we are to improve the therapeutic options available to patients.
The TLR field has become increasingly important with the advent of TLR based therapies to treat human diseases. Activation/inhibition of TLRs has been proposed to be beneficial for cancer, TB, HIV, vaccine development as well as the treatment of many autoimmune diseases, for example, lupus, rheumatoid arthritis and ulcerative colitis.
My research is performed in primary human cells and disease tissue where possible, as I believe this is essential to gain the closest insight into the mechanisms underlying human disease.
Key/recent publications:
Sandra Sacre, Mino Medghalchi, Bernard Gregory, Fionula Brennan and Richard Williams.(2009) The SSRIs fluoxetine and citalopram exhibit potent anti-inflammatory activity in human and murine models of rheumatoid arthritis and inhibit signalling via toll-like receptors. Arthritis and Rheumatism (in press).
Midwood K., Piccinini, A and Sacre S.M. Targeting toll-like receptors in autoimmunity (2009). Curr Drug Targets. Dec 1. [Epub ahead of print].
Kim Midwood, Sandra Sacre, Julia Inglis, Annette Trebaul, Emma Chan, Anna M. Piccinini, Stefan Drexler, Nidhi Sofat, Masahide Kashiwagi, Gertraud Orend, Fionula Brennan and Brian Foxwell (2009). Tenascin-C is an endogenous activator of TLR4 that is essential for maintaining inflammation in arthritic joint disease. Nat. Med.15:774-80.
Turner JJ, Smolinska MJ, Sacre SM, Foxwell BMJ (2009). Induction of TLR Tolerance in Human Macrophages by Adiponectin; Does Lipopolysaccharide Play a Role? Scand. J. Immunol. 69:329-36.
Sandra M. Sacre, Alexandra Lo, Bernard Gregory, Rachel Simmonds, Lynn Williams, Marc Feldmann, Fionula Brennan, and Brian M. Foxwell (2008) IInhibitors of toll-like receptor 8 reduce TNF production from human rheumatoid synovial membrane cultures. J. Immunol. 181:8002-9.
Lundberg AM, Drexler SK, Monaco C, Williams LM, Sacre SM, Feldmann M, Foxwell BM (2007). Key differences in TLR3/poly I:C signaling and cytokine induction by human primary cells: a phenomenon absent from murine cell systems. Blood, 110(9):3245-52.
Sacre SM, Lundberg AM, Andreakos E, Taylor C, Feldmann M, Foxwell BM (2007). Selective use of TRAM in lipopolysaccharide (LPS) and lipoteichoic acid (LTA) induced NF-kappaB activation and cytokine production in primary human cells: TRAM is an adaptor for LPS and LTA signaling. J Immunol. 15;178(4):2148-54.
Sandra M. Sacre, Evangelos Andreakos, Serafim Kiriakidis, Parisa Amjadi, Anna Lundberg, Grey Giddins, Marc Feldmann, Fionula Brennan, and Brian M. Foxwell (2007). The Toll-like receptor adaptor proteins MyD88 and Mal/TIRAP contribute to the inflammatory and destructive processes in a human model of rheumatoid arthritis. American J. Pathol. 170 (2), 518-25.
Sacre SM, Drexler SK, Andreakos E, Feldmann M, Brennan FM, Foxwell BM (2007).
Could toll-like receptors provide a missing link in chronic inflammation in rheumatoid arthritis? Lessons from a study on human rheumatoid tissue. Ann Rheum Dis. 66 Suppl 3:iii81-6. Stefan K Drexler,
Sandra M Sacre, Brian M Foxwell (2006) Toll-like receptors: a new target in rheumatoid arthritis? Expert Review of Clinical Immunology, July 2006, Vol. 2, No. 4, 585-599.
S.M. Sacre, M.J. Larche and B.M. Foxwell (2005) Pathogenic Role of TNFa in Rheumatoid Arthritis. Drug Discovery Today: Disease Mechanisms, 2: 367- 375.
Sacre SM, Andreakos E, Taylor P, Feldmann M, Foxwell BM (2005) Molecular therapeutic targets in rheumatoid arthritis. Expert Rev Mol Med.7:1-20.
Sacre SM, Drexler S, Foxwell BM (2005) Toll-like receptors and rheumatoid arthritis: is there a connection? In Toll-like Receptors in Inflammation. Eds: O'Neill L, Brint E. Birkhauser.
Evangelos Andreakos, Sandra Sacre, Brian M. Foxwell and Marc Feldmann (2005). The toll-like receptor-nuclear factor kB pathway in rheumatoid arthritis. Frontiers in Bioscience 10, 2478-2488
Sandra M Sacre, Evangelos Andreakos, Mark Feldmann and Brian M. Foxwell (2004). Endotoxin signaling in human macrophages: Signaling via an alternate mechanism. J. Endotoxin Res. 10:445-52.
Funding:
European Commission FP7 Masterswitch (Mechanisms to attack steering effectors of rheumatoid syndromes with innovated therapy choices) project. Active collaborations:
Dr Cathy Tralau-Stewart, Head of the Drug Discovery Centre (Imperial College London)
Prof. Alan Armstrong, Chemistry Department (Imperial College London)
Other information:
- Member of the Biochemical Society
- Member of the British Society for Cell Biology