Professor Corinne M. 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”.

I am currently leading the Horizon 2020 Innovative Training Network MASSTRPLAN, a collaborative project with 10 full partners and 15 associated partners that will train 14 early stage researchers in mass spectrometry and complementary techniques to study lipoxidation in biological and biomedical sciences. MASSTRPLAN started on the 1st October 2015 and will run until 30th September 2019.

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

• 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).

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, give key skills tutorials for BY1KS1 and BY2KS2 and contribute to the Final Year, MBiol and Masters research projects.

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.

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.

1. Analysis and Effects of 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, and improving methodology for ox-phospholipidomics continues to be a major focus. There are hundreds of different species of oxidized lipids and phospholipids, so selective, targeted approaches are needed to identify them in biological or clinical samples. Moreover, many oxidized lipids and phospholipids are reactive owing to the presence of carbonyl groups, and can form adducts with nucleophilic groups in proteins, a process called lipoxidation. Analysis of the products is very challenging, and is the focus of a new EU-funded project called MASSTRPLAN. It is also thought that lipoxidation is an important mechanism by which oxidized lipids cause some of their biological effects.
The study  of the biological effects of oxidized and chlorinated phospholipids is another research topic in the group.  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 age-related diseases such as cancer, cardiovascular disease and chronic kidney disease. We are also expanding the approach to look at lipid peroxidation product adducts with proteins, especially in LDL and ageing tissue, as described above.

3. Redox Signaling and Protein Oxidation

It is now understood that protein oxidation, especially at susceptible cysteine residues, is a mechanisms of regulation of enzyme activity and protein function. We have also been studying the effects of oxidation on protein-protein interactions, and reported for the first time how the interactome of the tumour suppressor protein PTEN changes when the PTEN is reversibly oxidized. Research is ongoing to characterize the oxidation and investigate the biological effects downstream of PTEN signaling.

4. Antimicrobial Mechanisms of Silver and Antimicrobial Resistance

Silver has been used as an antimicrobial agent for sterilizing water and topical treatment of infections for hundreds of years. The recent increase in the use of silver, especially in nanomaterials and smart materials, has enhanced the development of resistance. We are working with special chemical forms and formulations of silver to improve its antimicrobial action, and investigating the biochemical effects of silver containing complexes.

  Lead Investigator and Project coordinator of the EU funded innovative training network MASSTRPLAN: Mass Spectrometry Training Network for Protein Lipid Analysis. 

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)

Project Coordinator - H2020 ITN-ETN MASSTRPLAN (2015-2019)

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.

• Horizon 2020 ITN MASSTRPLAN: Mass Spectrometry TRaining Network for Protein Lipid ANalysis, (2015-2019) (click here to see the MASSTRPLAN web site)
• 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. 
• Mass Spectrometry Training Network for Protein Lipid Adduct Analysis (MASSTRPLAN). (2015-2019) H2020 ITN-ETN Project ID 675132. €3,545,010. PI, joint with Prof A.R. Pitt, Prof H.R. Griffiths and Dr J.E.P. Brown.

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

• Sabah Pasha: Sarcoplasmic reticulum proteins as models of protein oxidation in ageing (2011- submitted Sept 2015) LHS funded studentship (1^a supervisor).
• Stuart Calimport: Targetted mass spectrometry studies of protein oxidation in ageing and its relationship to function (2011- submitted Sept 2015) LHS funded studentship (2^a supervisor).
• Stuart Meredith: Translatable biotechnology for detecting protein oxidation and understanding its role in inflammation. (2012- submission for PhD expected summer 2016) 4-yr BBSRC-funded CASE Award (1^a supervisor).
• Alpesh Thakker: Method development for analysis of oxidised phospholipids using mass spectrometry technology. (2013- submission for PhD expected June 2016) LHS Overseas Bursary (1^a supervisor).
  

PhD Studentships / Early Stage Researcher Positions Available NOW (Jan 2016)

2 positions for early stage researchers (within 4 years of 1st degree) are available for research at Aston University on lipid and protein oxidation as part of the MASSTRPLAN project. Ideal for European students who are keen to travel and have a good background in biochemistry / chemistry/ cell biology. The researchers will be expected to register for PhD degrees. A further 12 positions are available at the other MASSTRPLAN organizations.See the MASSTRPLAN Recruitment webpage for further information (eligibity rules apply).

• 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)