Centre staff
Professor Nicola Woodroofe
Professor of neuroimmunology and head of the BMRC
Phone 0114 225 3065
Email n.woodroofe@shu.ac.uk
Research interests
Molecular pathology of neurological diseases
Research interests centre on neurological disease, in particular multiple sclerosis
(MS). Immunological events that occur within the central nervous system (CNS) during
the progression of MS are the primary focus of current studies; in particular the
role of chemokines and the metalloproteinase family of enzymes in disease pathogenesis.
It is hoped that this research will lead to the development of new therapeutics
targeting inflammatory mediators. The experimental approaches taken span from studies
on people with MS in collaboration with neurologists at Sheffield Teaching Hospitals
NHS Foundation Trust, to the cellular level assessing brain cells in culture.
The role of chemokines in the pathogenesis of multiple sclerosis
Chemokines are chemoattractant cytokines which are expressed in lesions within the
CNS and play a key role in cell recruitment to sites of inflammation. They are also
present within the cerebrospinal fluid of MS patients. Astrocytes within MS lesions
also express CCL2 and CXCL10 and their regulation by cytokines by these cells in
vitro is under investigation. Studies on chemokine truncation by metalloproteinases
and dipeptidyl peptidases and the effects of this on migration of monocytic cells
as well as determining the migration index of PBMCs from people with MS, before and
after initiation of immunomodulatory treatment, is increasing our understanding of
their role in MS pathogenesis.
The role of metalloproteinases in disease pathogenesis
Since TNF has been implicated in the pathological process in
MS we have investigated the expression of ADAM 17, also known as TACE,
which is the enzyme responsible for cleaving pro TNF into its active form.
Since ADAM 17 is responsible for shedding of a number of adhesion molecules
and cytokine receptors from the cell membrane in
vitro studies are underway to assess the functional role of ADAM 17 in MS pathogenesis.
Adenoviral vector knockdown of ADAM17 in the murine model of EAE is being used to
assess the effects of decreased ADAM17 expression in the CNS on the inflammatory
response. This work is in collaboration with Dr
Rowena Bunning, Professor Mimoun Azzouz, Department of Academic Neurology, University
of Sheffield and Dr Chris Bolton, Queen Mary's, London and is funded by the UK Multiple
Sclerosis Society.
Citrullination and MS pathogenesis
A project supported by a Multiple Sclerosis Society studentship is investigating
the role of citrullination, a post translational modification, of CNS proteins on
the disease pathogenesis and whether antibodies in the serum and/or cerebrospinal
fluid may provide a diagnostic indicator of multiple sclerosis. This is in collaboration
with Dr Alison
Cross, Dr Gail
Haddock and Dr Basil Sharrack (Sheffield
Teaching Hospitals NHS Foundation Trust).
Skin sensitisation
In collaboration with Professor
Malcolm Clench, we are assessing whether MALDI mass spectrometry imaging can
be used to distinguish an irritant or a sensitisation response in human skin.
- Transplant immunology
Several projects in collaboration with Dr Brendan Clark at the Transplant Immunology Department, St James's University Hospital, Leeds are focussed on improving transplant outcomes by a better understanding of the immune response to HLA mismatching. Specifically Richard Battle has been funded by the NIHR to undertake a full time PhD on the development of immuno-proteomic approaches to the assessment of tissue compatibility for transplantation
Collaborators
- Dr Brendan Clark, Transplant Immunology, St James's University Hospital, Leeds
- Dr Steve Howell, Neurology Department, Sheffield Teaching Hospital Foundation Trust
- Dr Sian Price, Neurology Department, Sheffield Teaching Hospital Foundation Trust
- Dr Basil Sharrack, Neurology Department, Sheffield Teaching Hospital Foundation Trust, Glossop Road, Sheffield
- Dr Julie Simpson, Academic Neurology, University of Sheffield
- Dr Steve Wharton, Academic Neurology, University of Sheffield
Recent publications
Hadjivassiliou, M Aeschilmann D, Grunewald, RA, Sanders, DS, Sharrack, B and Woodroofe, N. (2011) Acta Neurologica Scandinavica, 123, 175-180.
Hart, PJ Francese, S, Claude, E, Woodroofe, MN and Clench, MR (2011) MALDI-MS imaging of lipids in ex vivo human skin. Analytical and Bioanalytical Chemistry 401,115-125
Hadjivassiliou M, Sanders DS, Grunewald RA, Woodroofe MN, Boscolo S, Aeschilmann D (2010) Gluten sensitivity: from gut to brain. Lancet Neurology, 9: 318-330.
Dhungana S, Sharrack B, Woodroofe MN (2010) Idiopathic intracranial hypertension. Acta Neurologica Scandinavica, 121: 71-82.
Dhungana S, Waters P, Ismail A, Woodroofe N, Vincent A, Sharrack B (2010). Absence of aquaporin-4 antibodies in patients with idiopathic intracranial hypertension. Journal of Neurology, 257: 1211-1212.
Dhungana S, Sharrack B, Woodroofe N (2009) IL-1 beta, TNF and IP-10 in the cerebrospinal fluid and serum are not altered in patients with idiopathic intracranial hypertension compared to controls. Clinical Endocrinology, 71: 897.
Denney H, Clench MR, Woodroofe MN (2009) Cleavage of chemokines CCL2 and CXCL10 by matrix metalloproteinases-2 and -9: implications for chemotaxis. Biochemical and Biophysical Research Communications, 382(2): 341-347.
Hurst L.A., Bunning, R. A. D., Couraud, P-O., Romero, I. A., Weksler, B. B., Sharrack, B., Woodroofe, M. N.(2009) Expression of ADAM-17, TIMP-3 and fractalkine in the human adult brain endothelial cell line, hCMEC/D3, following pro-inflammatory cytokine treatment. J Neuroimmunol, 120 (1-2): 108-112.
Taylor D, Dalton C, Hall A, Woodroofe MN, Gardiner PHE (2009) Recent developments in selenium research. British Journal of Biomedical Science, 66(2): 107-116.
Bradford CM, Cross AK, Haddock G and Woodroofe MN. Citrullination in MS: Potential for a new diagnostic test (2009) British Journal of Neuroscience Nursing, 5 (1): 13-15.
Reid MJ, Cross AK, Haddock G, Allan SM, Stock CJ, Woodroofe MN. Buttle DJ, Bunning RAD (2009) ADAMTS-9 expression is up-regulated following transient middle cerebral artery occlusion (tMCAo) in the rat. Neuroscience Letters, 452: 252-257.
Dhungana S, Sharrack B, Woodroofe N (2009) Cytokines and chemokines in idiopathic intracranial hypertension. Headache, 49: 282-285.
Hadjivassiliou M, Aeschlimann P, Strigun A, Sanders D, Woodroofe N, Aeschlimann D (2008) Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase. Neurology, Volume 64, Issue 3, 332-343.
Hadjivassiliou N, Sanders DS, Woodroofe N, Williamson C, Grunewald RA (2008) Gluten ataxia. Cerebellum, 7: 494-498.
Hadjivassiliou M, Boscolo S, Tongiorgi E, Grunewald RA, Sharrack B, Sanders DS, Woodroofe MN, Davies GAB (2008) Cerebellar ataxia as a possible organ-specific autoimmune disease. Movement Disorders, 23: 1370-1377.
Haddock G, Cross AK, Plumb J, Surr J, Buttle DJ, Bunning RAD and Woodroofe MN. The expression of ADAMTS-1, -4, -5 and TIMP-3 in normal and multiple sclerosis CNS white matter. Multiple Sclerosis, 12(4): 386-96.
Cross AK, Haddock G, Surr J, Plumb J, Bunning RAD, Buttle DJ and Woodroofe MN (2006) Differential expression of ADAMTS-1, -4, -5 and TIMP-3 in rat spinal cord at different stages of acute experimental autoimmune encephalomyelitis. Journal of Autoimmunity, 26(1): 16-23.
Cross AK, Haddock G, Stock CJ, Allan S, Surr J, Bunning RAD, Buttle DJ, Woodroofe MN (2006) ADAMTS-1 and -4 are up-regulated following transient middle cerebral artery occlusion in the rat and their expression is modulated by TNF in cultured astrocytes. Brain Research, 1088: 19-30.
Plumb J, Cross AK, Surr J, Haddock G, Smith T, Bunning RAD, Woodroofe MN (2005) ADAM-17 and TIMP3 protein and mRNA expression in spinal cord white matter of rats with acute experimental autoimmune encephalomyelitis. Journal of Neuroimmunology, 164: 1-9.
Plumb J, McQuaid S, Cross AK, Surr J, Haddock G, Bunning RAD and Woodroofe MN (2005). Upregulation of ADAM-17 expression in active lesions in multiple sclerosis. Multiple Sclerosis. In Press.
Postdoctoral researchers
- Dr Melanie Sinagra-Viphakone
PhD students
- Claire Bradford (funded by the UK MS Society) - Role of citrullination of CMS proteins in the pathogenesis of multiple sclerosis
- Richard Battle (funded by the National Institute for Health Research) - Development of immuno-proteomic approaches to the assessment of tissue compatibility for transplantation
- Ruth Platt (part time at St James's University Hospital, Leeds) - When is the B cell response a good indicator of T cell allomemory?
- Philippa Hart (second supervisor) - Direct tissue profiling and imaging by Mass Spectrometry as a novel method for the investigation of the inflammatory signals induced.
- Rachel Waller (University of Sheffield, second supervisor) - Analysis of astrocyte transcriptome and proteome in multiple sclerosis lesions
DProf students
- Sharon Baker, Transfusion Practioner, Sheffield Teaching Hospitals NHS Foundation Trust
- John Barraclough, Haematology Department, Huddersfield Royal Infirmary
- Neil Marsden, Transplant Immunology, St James's University Hospital, Leeds
- Katherine Poole, Transplant Immunology, St James's University Hospital
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