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Professor Philip Eaton

Philip

Professor of Cardiovascular Biochemistry

Centre: Clinical Pharmacology and Precision Medicine

Email: p.eaton@qmul.ac.uk
Telephone: +44(0) 20 7882 6863

Profile

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 post-doctoral work at the Institute of Psychiatry, he joined the Department of Cardiovascular Research at the Rayne Institute, St Thomas’ Hospital in 1995. He remained there for nearly 24 years within the School of Cardiovascular Medicine & Sciences at King’s College London. In 2019, he moved to the William Harvey Research Institute, Queen Mary University of London where he heads a group studying the molecular basis of redox sensing and signalling in the cardiovascular system.

Research

Group members
Dr. Rebecca Charles (BHF Intermediate Fellow): Dr. Hyunju Cho; Dr. Mariana Fernandez-Caggiano; Dr. Lorena Fernandez-Mosquera; Dr. Asvi Francois; Dr. Alisa Kamynina; Dr. Gundeep Kaur; Dr. Oleksandra Prysyazhna; Dr. Daniel Simoes De Jesus; Dr. Christopher Switzer

Summary 

Oxidants, which can be produced in cells and tissues, have been causatively implicated in the pathogenesis of most major diseases. Whilst this paradigm is still prevalent, and oxidants may indeed play important roles in the disease etiology, it is now understood that they can also serve as regulatory entities that are important for the maintenance of homeostasis during health and disease. Oxidants can be sensed and transduced into a biological event via their reaction with select cysteine thiol side chains on some proteins. Such reactions can result in oxidative post-translational modifications of proteins that in some cases alter their function to enable adaptation and homeostasis. By identifying thiol-based redox sensor proteins susceptible to oxidant-dependent alterations in structure and function, it is hoped a better understanding of the biological significance of these modifications during cardiovascular health and disease can be gained. Indeed, in some cases we have developed new electrophilic drugs that modify precise redox regulated cysteines for therapeutic purposes to combat cardiovascular disease. 

Key Publications

Full list of publications

  1. Switzer CH, Cho H, Eykyn TR, Lavender P and Eaton P (2022). NOS2 expression and S-nitrosothiol signaling induces passive DNA demethylation and LINE-1 retrotransposon expression. Proc Nat Acad Sci USA. 119 (21) e2200022119.
  2. Kamynina A, Guttzeit S, Eaton P (joint corresponding author), Cuello F. (2022). Nitroxyl Donor CXL-1020 Lowers Blood Pressure by Targeting C195 in Cyclic Guanosine-3',5'-Monophosphate-Dependent Protein Kinase I. Hypertension 79:946–956.
  3. Switzer CH, Guttzeit S, Eykyn TR and Eaton P (2021). Cysteine trisulfide oxidizes protein thiols and induces electrophilic stress in human cells. Redox Biology 29;47:102155.
  4. Charles RL, Abis G, Fernandez BF, Guttzeit S, Buccafusca R, Conte MR and Eaton P (2021). A thiol redox sensor in soluble epoxide hydrolase enables oxidative activation by intra-protein disulfide bond formation. Redox Biology 46:102107.
  5. Fernandez-Caggiano M and Eaton P (2021). Heart failure - emerging roles for the mitochondrial pyruvate carrier. Cell Death and Differentiation doi: 10.1038/s41418-020-00729-0.
  6. Fernandez-Caggiano M, Kamynina A, Francois A, Prysyazhna O, Eykyn T, Krasemann K, Crespo-Leiro M, Garcia Vieites M, Bianchi K, Morales V, Domenech N, Eaton P (2020). Mitochondrial pyruvate carrier abundance mediates pathological cardiac hypertrophy. Nature Metabolism 2(11):1223-1231.
  7. Oxidation of PKGIα mediates an endogenous adaptation to pulmonary hypertension. Rudyk O, Rowan A, Prysyazhna O, Krasemann S, Hartmann K, Zhang M, Shah A. M, Ruppert C, Weiss A, Schermuly R. T, Ida T, Akaike T, Zhao L, and Eaton P (2019). Proc Nat Acad Sci USA. 116 (26): 13016-13025.
  8. Singlet molecular oxygen regulates vascular tone and blood pressure in inflammation (2019). Stanley CP, Maghzal GJ, Ayer A, Talib J, Giltrap AM, Shengule S, Wolhuter K, Wang Y, Chadha P, Suarna C, Prysyazhna O, Scotcher J, Dunn LL, Prado FM, Nguyen N, Odiba JO, Baell JB, Stasch JP, Yamamoto Y, Di Mascio P, Eaton P, Payne RJ, Stocker R. Nature 566: 548–552.
  9. Cysteine-Based Redox Sensing and Its Role in Signaling by Cyclic Nucleotide-Dependent Kinases in the Cardiovascular System. Cuello F, Eaton P (2019). Annu Rev Physiol. 10;81: 63-87.
  10. Wolhuter K, Whitwell H, Switzer C, Burgoyne J, Timms J and Eaton P (2018). Evidence against stable protein S-nitrosylation as a widespread mechanism of post-translational regulation. Molecular Cell 69(3): 438-450.
  11. Burgoyne J, Prysyazhna O, Richards D and Eaton P (2017). Proof of principle for a novel class of antihypertensives that target the Oxidative Activation of PKG Iα. Hypertension 70(3): 577-586.
  12. Scotcher J, Prysyazhna O, Boguslavsky A, Kistamas K, Hadgraft K, Martin E D, Worthington J, Rudyk O, Cutillas P. R, Cuello F, Shattock M J. , Marber M. S, Conte M R, Greenstein A, Greensmith D J, Venetucci L, Timms J F and  Eaton P (2016). Disulfide-activated protein kinase G Iα regulates diastolic relaxation of the heart and fine-tunes the Frank-Starling response. Nature Communications 7: 13187.
  13. Burgoyne JR, Rudyk O, Cho H, Prysyazhna O, Evans R, Ng T, Schröder K, Brandes RP, Shah AM, Eaton P (2015). Deficient angiogenesis in redox-dead Cys17Ser PKARIα knock-in mice. Nature Communications 6, article number:7920
  14. Charles RL, Rudyk O, Prysyazhna P, Kamynina A, Yang Y, Morisseau C, Hammock B, Freeman B, Eaton P (2014). Protection from hypertension in mice by the Mediterranean diet is mediated by nitro fatty acid inhibition of soluble Epoxide Hydrolase. Proc Nat Acad Sci USA 3;111(22): 8167-72.
  15. Stubbert D, Prysyazhna P; Rudyk O, Scotcher J, Burgoyne JR, Eaton P (2014). Protein kinase G Iα oxidation paradoxically underlies blood pressure lowering by the reductant hydrogen sulfide. Hypertension, 64(6): 1344-51
  16. Rudyk O, Phinikaridou A, Prysyazhna O, Burgoyne JR, Botnar R and Eaton P (2013). Protein kinase G oxidation is a major cause of injury during sepsis. Proc Nat Acad Sci USA 110(24): 9909-13.
  17. Burgoyne JR, Prysyazhna O, Rudy K, Eaton P (2012). cGMP-dependent activation of protein kinase G precludes disulfide activation: implications for blood pressure control. Hypertension, 60(5): 1301-1308.
  18. Rudyk O, Prysyazhna O, Burgoyne JR and Eaton P (2012). Nitroglycerin Fails to Lower Blood Pressure in Redox-Dead Cys42Ser PKG1α Knock-In Mouse. Circulation. 126(3): 287-95.
  19. Prysyazhna O, Rudyk O and Eaton P (2012). Single atom substitution in mouse protein kinase G eliminates oxidant sensing to cause hypertension. Nature Medicine. 18(2): 286-90.
  20. Charles RL, Burgoyne JR, Mayr M, Weldon SM, Hubner N, Dong H, Morisseau C, Hammock BD, Landar A and Eaton P (2011). Redox regulation of soluble epoxide hydrolase by 15d PGJ2 controls coronary hypoxic vasodilation. Circulation Research 108(3): 324-34.
  21. Burgoyne JR, Madhani M, Cuello F, Charles RL, Brennan JP, Schröder E, Browning DD and Eaton P (2007). Cysteine redox sensor in PKGIα enables oxidant-induced activation without nitric oxide pathway. Science 317: 1393-1397.
  22. Saurin AT, Neubert H, Brennan JP and Eaton P. (2004). Widespread sulfenic acid formation in tissues in response to hydrogen peroxide. Proc Nat Acad Sci USA 101(52): 17982-7.

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