.

Dr Corinne Spickett

 

Reader in Biosciences

Research Theme

Chronic and Communicable Conditions

Research Centre

Aston Research Centre for Healthy Ageing (ARCHA) 

Dr Corinne Spickett
I joined the School of Life and Health Sciences in January 2011, after 17 years as an academic member of staff at the University of Strathclyde. I worked in several different departments there, starting in Chemistry, then moving to Immunology, Bioscience, and lastly Strathclyde Institute of Pharmacy and Biomedical Science. This reflects my broad scientific background and interests in oxidative stress ranging from molecular processes to inflammation in disease.

I have extensive collaborations in Europe: currently I am treasurer of the Society for Free Radical Research (Europe), a workgroup leader in the COST Action CM1001 on “Chemistry of non-enzymatic protein modification”, and a member of the International HNE-Club committee, having just stood down as secretary.

I have taught extensively in biological and biomedical related classes at the University of Strathclyde, where my primary focus was on biochemistry, metabolism and molecular events in cardiovascular disease. I have also been an invited lecturer for the Masters in Integrative Physiology at the University of Barcelona, and have lectured at the Spetses Free Radical Summer School run by the Society of Free Radical Research Europe.

Qualifications & Education

  • BA (Hons) Biochemistry  - Oxford University (Pembroke College) - 1986
  • DPhil Biochemistry - Oxford University (Pembroke College) - 1990
  • MA  - Oxford University (Pembroke College) - 1990  

Employment

  • August 2006 - January 2011: Senior Lecturer, SIPBS, University of Strathclyde.
  • April 2005 - August 2006: Senior Lecturer, Department of Bioscience, University of Strathclyde.
  • September 2001 – April 2005: Lecturer, Department of Bioscience, University of Strathclyde.
  • September 1994 - August 2001: Glaxo-Jack Research Lecturer, Department of Immunology, University of Strathclyde.
  • April 1993 - to August 1994:  SHHD funded postdoctoral research fellow in the Dept. of Pure and Applied Chemistry, Strathclyde, working with Prof. W.E. Smith. (An investigation of oxidative stress in preeclamptic erythrocytes using in vivo NMR and resonance Raman spectroscopy).
  • April 1992 - March 1993:  AFRC funded postdoctoral research assistant to Dr C. Abell, Department of Chemistry, Cambridge. (The purification of kaurene synthase and related diterpene cyclases from Ricinus communis).
  • October 1989 - March 1992:  AFRC funded postdoctoral research assistant to Dr B.C. Loughman and Dr R.G. Ratcliffe, Department of Plant Sciences, Oxford. (The application of in vivo NMR to the study of plant systems).

Teaching activity

Here at Aston University, I am currently only involved in teaching key skills tutorials for BY1KS1 and BY2KS2.  However, previously at the University of Strathclyde I taught a wide range of lecture- and laboratory-based classed, mainly in the biochemistry and biomedical science areas.

Research interests

All my current research is in the field of oxidative stress. I have been working on this subject since 1994, when I moved to the University of Strathclyde.  Oxidative stress occurs when the level of free radicals or oxidants in a system exceeds the capacity of antioxidants to protect against them.  This can lead to oxidative damage, thus harming the cell or tissue. This often happens in inflammation, which occurs in infectious diseases as well chronic diseases such as cardiovascular disease, diabetes, cancer, and neurodegenerative diseases.  These diseases are a major cause of ill-health and mortality in all developed countries, and increasingly in developing countries.

Oxidants are formed in many metabolic and environmental processes.  They are also be released by phagocytes during their role in early immune defence against pathogens, but in severe inflammation may result in host tissue damage and pathology. I am interested in various aspects of oxidant metabolism, from mechanisms of cell killing by oxidants and cell antioxidant defence to the role of immune cell-derived oxidants in disease and immunomodulatory effects of oxidised macromolecules.  Much of the research in my group relates to cardiovascular disease (CVD) and atherosclerosis, conditions where oxidative stress is clearly implicated in the pathology of the disease, through the increased cellular uptake of oxidized low density lipoprotein (LDL). One of the major techniques used is electrospray mass spectrometry (ESMS), which can be applied to the analysis of phospholipid and protein oxidation. Together with Prof Andy Pitt, we are currently establishing a new, state-of-the-art mass spectrometry facility in Life and Health Sciences.


Specific Research Areas

1. Oxidized and Chlorinated Phospholipids

Polyunsaturated phospholipids are particularly susceptible to oxidation by free radicals and also by the phagocyte-derived oxidant hypochlorous acid (HOCl). In early work we developed liquid chromatography electrospray mass spectrometry as an informative method for detecting specific oxidized phospholipids both in LDL and cells. Improving methodology for ox-phospholipidomics is still an area of interest, but the major focus now is on the biological effects of oxidized and chlorinated phospholipids.  The responses of cells to lipid oxidation products such as oxPAPC, oxysterols, chlorohydrins of phosphatidylcholine and 4-HNE are have been investigated in cultured cells and a physiological model of vascular cell adhesion.  We are especially interested in the way these compounds are recognized by cells, and the balance of pro-inflammatory versus anti-inflammatory effects. We have also been working on the biophysical effects of these compounds on biological membranes.

2. Novel MS methodology for detecting protein oxidation

Protein oxidation causes cellular dysfunction and is thought to contribute to a variety of chronic diseases.  We have been developing advanced mass spectrometry (MS) methodologies for detecting specific types of oxidative protein damage, for example by hypochlorous acid or peroxynitrite, using MS2 and MS3 precursor ion scanning techniques. We are currently interested in applying this to protein dysfunction in ageing and arthritis. We are also expanding the approach to look at lipid peroxidation product adducts with proteins, especially in LDL and ageing tissue. This is currently a major focus of my research.

3. Effects of oxychloro compounds on cells

Oxidants similar to those released by phagocytes are also used as preservatives in many preparations for ocular application, e.g. sodium chlorite (NaClO2). Previously, we have looked at the differential effects of oxidants and other preservatives on ocular cells and pathogens, with a focus on understanding the basis of antimicrobial action and mammalian cell toxicity.  We are currently using Saccharomyces cerevisiae as a model to investigate the role of antioxidants in protection against oxychloro compounds (HOCl and NaClO2) in a collaborative project with Prof Grzegorz Bartosz in Poland. 


Recent / Current European Roles and Collaborations


International HNE-Club - Secretary 2004-10, Committee member 2010

COST Action B35 on Lipid Peroxidation Associated Disorders - Management Committee and Workgroup Leader 2006-10

Society for Free Radical Research-Europe - Treasurer 2009-12

08-EuroMEMBRANES-FP-021: Molecular level physiology and pathology of oxidized phospholipids (2009-12). Associated Partner.

COST Action CM1001 on Chemistry of non-enzymatic protein modification - modulation of protein structure and function - Management Committee and Workgroup Leader (2010-2014)


Recent research funding

Funding for my research has come from a variety of sources, including research councils (BBSRC), charities (British Heart Foundation; Tenovus Scotland), government (Chief Scientist Office Scottish Exectutive; EU), and industry (Allergan Inc. USA).  I also collaborate extensive within Europe and am involved in several consortia. Significant recent awards (all at University of Strathclyde) are listed below.
  • Developing chemical agents for monitoring oxidative stress and inflammatory processes (2004-2007).  BBSRC (BBS/B/01553).  Joint with Dr John Reglinski, Department of Pure and Applied Chemistry.
  • New Detection Methods for Biomarkers of Protein Oxidation (2007).  BBSRC (BB/E015484/1) Joint with Dr A.R. Pitt at Glasgow University.
  • Involvement of chlorinated lipids in neointima formation (2009-2012). BHF PhD Studentship (FS/08/071/26212) Joint with Dr Simon Kennedy at Glasgow University.
  • 08-EuroMEMBRANES-FP-021: Molecular level physiology and pathology of oxidized phospholipids (2009-12). This European consortium of 11 teams has been recommended for funding by the European Science Foundation. Unfortunately, as the UK research councils did not subscribe to EuroMEMBRANES, I could not be a principal investigator. As an associated partner, funding will come to my group indirectly, via collaboration with the funded teams.
  • Identification of phospholipid-Apo B adducts in atherosclerosis by a mass spectrometry approach (2010-2012). FP7-PEOPLE-2009-IEF Project ID 255076.  Marie Curie Intra European Fellowship for Ana Reis Pereira.
  • Next Generation Analytical Tools: Application to Protein Oxidations that affect Human Health and Wellbeing (2011-2013). EP/I017887/1 Cross-Disciplinary Research Landscape Award.
GA ERDF Logo

PhD Supervision

I have supervised 16 graduate research students and more than a dozen visiting scientists from a variety of countries.  Currently I am supervising 2 PhD students and an MRes student who are still based in Glasgow.

  • Adishesha Ramaiah: Analysis of lipid peroxidation in biological samples (2008- , MRes)
  • Norsyhida Mohd Fauzi: Leukocyte-derived products in mechanisms and biomarkers of atherosclerotic processes  (2008-2011, PhD) funded by a scholarship from the Malaysian Government. Joint supervised with Prof Robin Plevin and Dr Paul Coats at University of Strathclyde.
  • Fiona Helen Greig: Involvement of chlorinated lipids in neointima formation (2009-2012, PhD) BHF PhD Studentship. Joint supervised with Dr Simon Kennedy at Glasgow University.

Currently I have projects available in the following areas of oxidative stress research:

  • Novel mass spectrometry methodology for analysis of protein oxidation in health and disease.
  • Mass spectrometry and lipidomic methodology.
  • Biological effects of oxidized and chlorinated lipids.

Membership of Professional Bodies

  • The Biochemical Society (1986-present)
  • Society for Free Radical Research (1995-present)
  • Society for General Microbiology (1997-present)
  • British Society for Cardiovascular Research (2003-present)

Selected recent publications

  • Advances in methods for the determination of lipid peroxidation products. Spickett CM, Wiswedel I, Siems W, Zarkovic K, Zarkovic N. (2010) Free Radic Res 44(10): 1172-1202.
  • Results of an interlaboratory validation of methods of lipid peroxidation measurements. Breusing N, Grune T, Andrisic L, Atalay M, Bartosz G, Biasi F, Borovic S, Bravo L, Casals I, Casillas R, Dinischiotu A, Drzewinska J, Faber H, Mohd Fauzi N, Galecka A, Gambini J, Gradinaru D, Kokkola T, Lojek A, Łuczaj W, Margina D, Mascia C, Mateos R, Meinitzer A, Mitjavila MT, Mrakovcic L, Munteanu MC, Podborska M, Poli G, Sicinska P, Skrzydlewska E, Vina J, Wiswedel I, Zarkovic N, Zelzer S,  Spickett CM. (2010) Free Radic Res Free Radic Res 44(10): 1203-1215.
  • Effect of phosphatidylcholine chlorohydrins on the erythrocyte Robaszkiewicz A, Spickett CM, Bartosz G, Soszyński M. (2010) Chem Phys Lipids 163(7): 639-647.
  • Protein oxidation: role in signalling and detection by mass spectrometry. Spickett CM and Pitt AR. (2010) Amino Acids, EPub April 2010.
  • Modulation of SERCA in the chronic phase of adjuvant arthritis as a possible adaptation mechanism of redox imbalance. Strosova M, Tomaskova I, Karlovska J, Spickett CM, Orszagova Z, Ponist S, Bauerova K, Mihalova D, HORAKOVA L. (2009)  Free Radic Res 43 (9): 852-864. 
  • Development of novel mass spectrometric methods for identifying HOCl-induced modifications to proteins. Mouls L, Silajdzic E, Haroune N, SPICKETT CM, Pitt AR. (2009) Proteomics 9 (6): 1617-1631. Oxidised phospholipid inhibition of Toll-like receptor (TLR) signalling is restricted to TLR2 and TLR4 - roles for CD14, LPS-binding protein and MD2 as targets for specificity of inhibition. Erridge C, Kennedy S, Webb DJ, SPICKETT CM (2008) J. Biol. Chem. 283(36):24748-59.
  • Copper N2S2 Schiffs base macrocycles: the effect of structure on redox potential. Taylor MK, Trotter KD, REGLINSKI J, Berlouis LEA, Kennedy AR, Spickett CM, Sowden RJ (2008) Inorgan Chim Acta 361 (9-10): 2851-2862.
  • Phospholipid chlorohydrin induces leukocyte adhesion to ApoE(-/-) mouse arteries via upregulation of P-selectin.  Dever GJ, Benson R, Wainwright CL, Kennedy S, SPICKETT CM.  Free Radic Biol Med. (2008) 44: 452-463.
  • A high fat meal induces low-grade endotoxemia: evidence for a novel mechanism of postprandial inflammation. ERRIDGE C, Attina T, Spickett CM, Webb DJ. (2007) Am J Clin Nutr. 86(5):1286-92.
  • Chlorinated lipids and fatty acids:  An emerging role in pathology. SPICKETT CM (2007) Pharmacol Therapeutics 115: 400-407
  • Non-enterobacterial endotoxins stimulate human coronary artery but not venous endothelial cell activation via Toll-like receptor 2. ERRIDGE C, Spickett CM, Webb DJ. (2007) Cardiovasc Res. 73(1): 181-9. The NO-donating pravastatin derivative (NCX 6550) reduces Splenocyte Adhesion and ROS Generation in Normal and Atherosclerotic Mice Dever, G., Spickett, C.M., Kennedy, S., Rush, C., Tennant, G., Monopoli, A. & Wainwright, C.L. (2007) J. Pharmacol. Exp. Therapeut., 320: 419-26.
  • Toll-like receptor 4 signalling is neither sufficient nor required for oxidised phospholipid mediated induction of interleukin-8 expression. Erridge, C.B., Webb, D.J. and SPICKETT, C.M. (2007) Atherosclerosis, 193(1) 77-85.
  • Proteomic Analysis of Phosphorylation, Oxidation and Nitrosylation in Signal Transduction. Spickett, C.M., Pitt, A.R., Morrice, N. and KOLCH, W. (2006) BBA Proteins and Proteomics, 1764(12): 1823-41.
  • A Comparison of the Effects of Ocular Preservatives on Mammalian and Microbial ATP and Glutathione Levels.  Ingram, P.R., Pitt, A.R., Wilson, C.G., Olejnik, O. and SPICKETT, C.M. (2004) Free Radic. Res. 38, 739-750.
  • Fatty acid composition, antioxidants and lipid oxidation in chicken breast of different product categories. Jahan, K., PATERSON, A., and Spickett, C.M. (2004) Int. J. Food Sci. Technol. 39, 443-453. (This publication led to a Radio 4 interview in December 2006.)

Employable Graduates; Exploitable Research