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Dr Corinne Spickett

 

Reader in Biosciences, Fellow of the Society of Biology

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 have a broad scientific background and interests in redox biology and 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), and a member of the International HNE-Club committee. I have been a Workgroup leader in 2 COST Actions: B35 on "Lipid Peroxidation in Health and Disease", and CM1001 on “Chemistry of non-enzymatic protein modification”.

Qualifications & Education

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

Previous 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

I have taught extensively on biochemistry, metabolism, proteins and enzymes, and molecular events in cardiovascular disease. I lecture regularly at the University of Barcelona for their Masters in Integrative Physiology, and have also lectured at the Spetses Free Radical Summer School run by the Society of Free Radical Research Europe.

At Aston University, I am module leader for Molecular Pathology and Cancer (BY2PA2 and EA3PA2) and for the masters level module Oxidative Stress and Inflammatory Disease. I also teach in modules on Nutrition and Biological basis of human disease, and give key skills tutorials for BY1KS1 and BY2KS2.

I am responsible for Continuing Professional Development in the shape of Top-up modules for Biomedical Science Accreditation, and recently developed a distance-learning version of these modules.

Research interests

My research is focused in the field of redox biology and oxidative stress.   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. Oxidative stress and damage is also an important factor in toxicology and adverse drug reactions, which can cause modification of proteins and

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. We are developing new mass spectrometry-based approaches to analysing and studying both lipid and protein oxidation in cells and tissues.

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.
  • Involvement of chlorinated lipids in neointima formation (2009-2012). BHF PhD Studentship (FS/08/071/26212) Joint with Dr Simon Kennedy at Glasgow University.
  • 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 (2011-2016). EP/I017887/1 Cross-Disciplinary Research Landscape Award. Joint with Prof Andrew Pitt.
  • European Research Development Framework “Promoting Biomarker Development in West Midlands SME's”. (2011-2015)Joint with Prof Helen R. Griffiths, Prof Andrew R Pitt, Prof Anthony Hilton.

  • Translatable biotechnology for detecting oxidative amino acid modifications and understanding of the role of radicals in inflammation. (2012-2016) BBSRC Industrial CASE Award BB/J012939/1. 
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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)
  • Society for Free Radical Biology and Medicine (2010-present)
  • Society of Biology (Fellow, 2013-present)

Recent publications(since 2013)

  • Interfacing low-energy SAW nebulization with Liquid Chromatography-Mass Spectrometry for the analysis of biological samples. Tveen-Jensen K, Gesellchen F, Wilson R, Spickett CM, Cooper JM and Pitt AR (2015) Sci Reports In press
  • Mass Spectrometry-Based Methods for Identifying Oxidized Proteins in Disease: Advances and Challenges. Verrastro I, Pasha S, Tveen-Jensen K, Pitt AR and Spickett CM (2015) Biomolecules 5: (2):378-411
  • Exploring oxidative modifications of tyrosine: An update on mechanisms of formation, advances in analysis and biological consequences. Houée-Lévin C, Bobrowski K, Horakova L, Karademir B, Schöneich C, Davies MJ, Spickett CM (2015) Free Radic Res. 49(4):347-73.
  • Oxidative Lipidomics Coming of Age: Advances in Analysis of Oxidized Phospholipids in Physiology and Pathology. Spickett CM, Pitt AR (2015) Antioxid Redox Signal. Mar 26. [Epub ahead of print]
  • Differential effects of chlorinated and oxidized phospholipids in vascular tissue: implications for neointima formation. Greig FH, Hutchison L, Spickett CM and Simon Kennedy S. (2015) Clin. Sci. 128(9):579-92.
  • Top-down lipidomics of low density lipoprotein reveal altered lipid profiles in advanced chronic kidney disease. Reis A, Rudnitskaya A, Chariyavilaskul P, Dhaun N, Melville V, Goddard J, Webb DJ, Pitt AR, Spickett CM. (2015)  J Lipid Res. 56(2):413-22
  • Identification and relative quantification of tyrosine nitration in a model Peptide using two-dimensional infrared spectroscopy. Rezende Valim L, Davies JA, Tveen Jensen K, Guo R, Willison KR, Spickett CM, Pitt AR, Klug DR. (2014) J Phys Chem B. Nov 13;118(45):12855-64.
  • Oxidised LDL-lipids increase beta amyloid production by SH-SY5Y cells through glutathione depletion and lipid raft formation. Dias IH, Mistry J, Fell S, Reis A, Spickett CM, Polidori MC, Lip GY, Griffiths HR. (2014) Free Radic Biol Med. 75:48-59
  • HOCl-modified phosphatidylcholines induce apoptosis and redox imbalance in HUVEC-ST cells Archives of Biochemistry and Biophysics. Robaszkiewicz A, Bartosz G, Pitt AR, Thakker A, Armstrong RA, Spickett  CM, Soszyński M (2014) Arch Biochem Biophys 548:1-10.
  • Detection of phosphatidylserine with a modified polar head group in human keratinocytes exposed to the radical generator AAPH. Maciel E, Neves  BM, Santinha D, Reis A, Domingues P, Cruz MT, Pitt AR, Spickett CM, Domingues MRM (2014) Arch Biochem Biophys 548:38-45.
  •  Post-translational Modifications and Mass Spectrometry Detection. Silva AM, Vitorino R, Domingues MR, Spickett CM, Domingues P. (2013) Free Radic Biol Med. 65: 925-41.
  • Joint Lipoxidation adducts with peptides and proteins: Deleterious modifications or signaling mechanisms? Domingues RM, Domingues P, Melo T, Pérez-Sala D, Reis A, Spickett CM. J Proteomics. 2013 92: 110-131.
  • Impairment of calcium ATPases by high glucose and potential pharmacological protection. Horakova L, Strosova MK, Spickett CM, Blaskovic D (2013) Free Radic Res. 47 Suppl 1: 81-92.
  • A comparison of five lipid extraction solvent systems for lipidomic studies of human LDL. Reis A, Rudnitskaya A, Blackburn GJ, Fauzi NM, Pitt AR, Spickett CM.J Lipid Res. 2013 54(7):1812-24.
  • Specific Lipidome Signatures in Central Nervous System from Methionine-Restricted Mice. .Jové M, Ayala V, Ramírez-Núñez O, Naudí A, Cabré R, Spickett CM, Portero-Otín M, Pamplona R. J Proteome Res. 2013 12(6): 2679-89.
  • Reporter ion-based mass spectrometry approaches for the detection of non-enzymatic protein modifications in biological samples. Tveen-Jensen K, Reis A, Mouls L, Pitt AR, Spickett CM. J Proteomics. 2013 Apr 17. doi:pii: S1874-3919(13)00180-2. 10.1016/j.jprot.2013.03.033.
  • The use of narrow mass-window, high-resolution extracted product ion chromatograms for the sensitive and selective identification of protein modifications. Spickett CM, Reis A, Pitt AR. Anal Chem. 2013 54(7):1812-24.
  • The lipid peroxidation product 4-Hydroxy-2-nonenal: advances in chemistry and analysis. Spickett C.M. (2013) Redox Biol 1(1): 145-152.
  • Reactions of copper macrocycles with antioxidants and HOCl: potential for biological redox sensing. Sowden RJ, Trotter KD, Dunbar L, Craig G, Erdemli O, Spickett CM, Reglinski J. (2013) Biometals 26(1) 85-96.

Most Cited 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.
  • Protein oxidation: role in signalling and detection by mass spectrometry. Spickett CM and Pitt AR. (2012) Amino Acids, 42(1): 5-21.
  • 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.
  • 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
  • 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.

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