Summary of discussion with Professor Philip Eaton, Professor of Cardiovascular Biochemistry at the Rayne Institute, St Thomas’ Hospital
On a mild morning in October, I caught up with Phil at the Rayne Institute, situated within St Thomas’ Hospital, London. Phil’s group works on cardiovascular biochemistry & specifically redox signalling systems. He has been at the Rayne for the last 18 years & his research there has contributed to the shift in thinking that oxidants may not always be bad for us. They are actually produced in healthy systems & may act as regulatory signals to help the heart & blood vessels adapt to disease. Indeed, many large scale trials with anti-oxidants such as vitamin E or beta carotene have failed to show benefits for ischaemic heart disease. Oxidants may therefore not cause damage, but send out signals that help the body to adapt to stress.
Phil’s group is studying known redox sensor proteins as well as identifying a variety of novel candidates using normal & diseased samples. He utilises a variety of proteomic, biochemical, cell biology & transgenic systems to identify not just native proteins but also to look at amino acid residues that are sensitive to oxidation.
While some antibodies to redox sensor proteins are available, he has recently worked with Cambridge Research Biochemicals (CRB) to generate specially modified peptide immunogens leading to a range of novel affinity-purified antibodies for his research work. Although there are many Companies that can produce antibodies, the real challenge is to characterise a good antibody for future translational work. Phil feels that while antibody generation is expensive, it is negligible compared with the costs associated with the years of work that follows on afterwards. He cites the strong word-of-mouth reputation that CRB have both in UK & Europe, together with their professionalism & quality of their peptide biochemists.
He hasn’t yet published with the novel antibodies, but is very encouraged that pilot data from one has already led to specific grant funding from the British Heart Foundation. This will provide a better understanding of not only the biochemistry & physiology of the healthy cardiovascular system, but also develop knowledge of why things go wrong in disease.
Heading out into the main St Thomas’ Hospital after chatting with Phil, I was struck by the value of having research teams so close to the clinical facilities & the patient population. Although highly specific antibody tools, these redox state antibodies might one day play a major role as clinical diagnostics or therapeutics.
Philip Eaton gained a BSc in Biochemistry from Queen Mary College, University of London in 1989 before completing his PhD studies at the University of Sussex. After a post-doctoral at the Institute of Psychiatry, he joined the Department of Cardiovascular Research, based at the Rayne Institute, St Thomas’ Hospital. Nearly twenty years on, he remains at the Rayne within the Cardiovascular Division of Kings’s College, London.
Review: Mechanisms of redox signalling in cardiovascular disease
Charles R.L., Burgoyne J.R. and Eaton P.
Chapter 2 in: Studies on Cardiovascular disorders. Oxidative Stress in Applied Basic Research and Clinical Practice. H.Sauer et al (eds.)
Springer Science and Business Media, LLC 2010
Prysyazhna O, Rudyk O, Eaton P. Single atom substitution in mouse protein kinase G eliminates oxidant sensing to cause hypertension. Nat Med. 2012; 18:286-290.
Rudyk O, Prysyazhna O, Burgoyne JR, Eaton P. Nitroglycerin fails to lower blood pressure in redox-dead Cys42Ser PKG1α knock-in mouse. Circulation. 2012; 126:287-295.
Charles RL, Burgoyne JR, Mayr M, Weldon SM, Hubner N, Dong H, Morisseau C, Hammock BD, Landar A and Eaton P. Redox regulation of soluble epoxide hydrolase by 15-deoxy-Δ-prostaglandin J2 controls coronary hypoxic vasodilation. Circ Res. 2011; 108(3):324-34.
Maller C, Schröder E, Eaton P. Glyceraldehyde 3-phosphate dehydrogenase is unlikely to mediate hydrogen peroxide signaling: studies with a novel anti-dimedone sulfenic acid antibody. Antioxid Redox Signal. 2011; 14(1):49-60.
Burgoyne JR, Rudyk O, Mayr M, Eaton P. Nitrosative protein oxidation is modulated during early endotoxemia. Nitric Oxide. 2010; 25(2): 118-124.
Burgoyne JR and Eaton P. A rapid approach for the detection, quantification, and discovery of novel sulfenic acid or S-nitrosothiol modified proteins using a biotin-switch method. Methods Enzymol 2010; 473:281-303.
Burgoyne JR and Eaton P. Transnitrosylating nitric oxide species directly activate Type I PKA providing a novel adenylate cyclase-independent crosstalk to beta-adrenergic like signaling. J Biol Chem. 2009; 284, 29260-29268.
Schröder E and Eaton P. Cardiac peroxiredoxins undergo complex modifications during oxidant stress. Am J Physiol (Heart) 2008; 295, 425-433.
Schröder E and Eaton P. Hydrogen Peroxide as an endogenous mediator and exogenous tool in cardiovascular research: issues and considerations. Current Opinion Pharmacol 2008; 8, 153-9.
Burgoyne JR, Madhani M, Cuello F, Charles RL, Brennan JP, Schröder E, Browning DD and Eaton P. Cysteine Redox Sensor in PKGIa Enables Oxidant-Induced Activation. Science 2007;317:1393-1397.