个人简介

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).

研究领域

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.

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.

近期论文

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Reversible oxidation of phosphatase and tensin homolog (PTEN) alters its interactions with signaling and regulatory proteins. Verrastro I, Tveen-Jensen K, Woscholski R, Spickett CM, Pitt AR. Free Radic Biol Med. (2016) Jan 90: 24-34. The hypotensive effect of acute and chronic AMP-activated protein kinase activation in normal and hyperlipidemic mice. Greig FH, Ewart MA, McNaughton E, Cooney J, Spickett CM, Kennedy S (2015) Vascul Pharmacol. Nov 74:93-102. Copper complexes as a source of redox active MRI contrast agents. Dunbar L, Sowden RJ, Trotter KD, Taylor MK, Smith D, Kennedy AR, Reglinski J, Spickett CM (2015) Biometals. Oct 28(5):903-12. Protein lipoxidation: detection strategies and challenges. Aldini G, Domingues MR, Spickett CM, Domingues P, Altomare A, Sánchez-Gómez FJ, Oeste CL, Pérez-Sala D (2015) Redox Biol May 5:253-266. 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, Sch?neich 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-Nú?ez 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.