Dr Rebecca Charles
BHF Intermediate Research Fellow
Centre: Clinical Pharmacology and Precision Medicine
Email: r.charles@qmul.ac.uk
Telephone: +44(0) 20 7882 6865
Profile
Rebecca gained a BSc in Biochemistry from The University of Birmingham in 2002 before working at Unilever for 3 years, where she was involved in a variety of different skin ageing and skin health projects including a number of clinical trials. Rebecca then undertook her PhD studies within the School of Cardiovascular Medicine & Sciences at King’s College London. In 2017, Rebecca received a BHF Intermediate Fellowship to investigate activation of soluble Epoxide Hydrolase by intra-protein disulfide formation. In 2019, she moved to the William Harvey Research Institute, Queen Mary University of London where her group studies the molecular basis of redox sensing and signalling in soluble epoxide hydrolase and its importance to the cardiovascular and pulmonary systems.
Research
Soluble epoxide hydrolase (sEH) is ubiquitously expressed, including in cardiovascular-relevant tissues such as endothelial or vascular smooth muscle cells as well as cardiomyocytes, where it is an important modulator of arterial and cardiac functions. sEH is also a susceptibility factor for human heart failure, with polymorphisms that enhance hydrolase activity increasing cardiovascular risk. Conversely, inhibitors (or transgenic knock-outs) of sEH offer a broad spectrum of cardiovascular protection, including blockade of smooth muscle proliferation, reduction of atherosclerosis and hypertension, prevention and regression of cardiac hypertrophy and HF, and fibrosis. Until 2009, little was known about how sEH activity was regulated and it was thought to be principally determined by its expression abundance. However, it is now apparent that a number of different oxidative post-translational modifications regulate this hydrolase. My research focuses on defining and understanding the molecular basis of redox sensing and signalling in sEH and its importance to the cardiovascular and pulmonary systems.
Publications
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de Jesus DS, Buffonge S, Abis G et al. (2024). Zinc-mediated inhibition of soluble epoxide hydrolase promotes pulmonary hypertension.
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Faulkes CG, Eykyn TR, Miljkovic JL et al. . Naked mole-rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestyles.
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Caggiano MF, Charles R, Prysyazhna O et al. (2023). UK-5099 does not inhibit the mitochondrial pyruvate carrier through irreversible adduction to cysteine 54 in MPC2.
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Charles R, Fernandez-Caggiano M, Rudyk O et al. (2022). A novel inhibitor of soluble Epoxide Hydrolase that adducts C521 is cardioprotective.
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Charles R, Eaton P . Redox Regulation of Soluble Epoxide Hydrolase—Implications for Cardiovascular Health and Disease.
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Charles RL, Abis G, Fernandez BF et al. (2021). A thiol redox sensor in soluble epoxide hydrolase enables oxidative activation by intra-protein disulfide bond formation.
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Cho H-J, Switzer CH, Kamynina A et al. (2020). Complex interrelationships between nitro-alkene-dependent inhibition of soluble epoxide hydrolase, inflammation and tumor growth.
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Abis G, Charles RL, Kopec J et al. . 15-deoxy-Δ12,14-Prostaglandin J2 inhibits human soluble epoxide hydrolase by a dual orthosteric and allosteric mechanism.
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Dunham-Snary KJ, Wu D, Potus F et al. (2019). Ndufs2, a Core Subunit of Mitochondrial Complex I, Is Essential for Acute Oxygen-Sensing and Hypoxic Pulmonary Vasoconstriction.
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Abis G, Charles RL, Eaton P et al. (2019). Expression, purification, and characterisation of human soluble Epoxide Hydrolase (hsEH) and of its functional C-terminal domain.
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Bassi R, Burgoyne JR, DeNicola GF et al. (2017). Redox-dependent dimerization of p38α mitogen-activated protein kinase with mitogen-activated protein kinase kinase 3.
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Charles RL, Rudyk O, Prysyazhna O et al. (2014). Protection from hypertension in mice by the Mediterranean diet is mediated by nitro fatty acid inhibition of soluble epoxide hydrolase.
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Charles RL, Rudyk O, Prysyazhna O et al. (2013). PSS135 Loss of Redox Regulation in Cys521Ser Soluble Epoxide Hydrolase Knock-In Mice Results in Hypertension and Hypertrophy.
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Charles R, Jayawardhana T, Eaton P (2014). Gel-based methods in redox proteomics.
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Charles R, Yin X, Mayr M et al. (2012). Detection and Identification of Cardiac Proteins Modified by the Dietary Flavanol Curcumin.
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Schroder E, Prysyazhna O, Charles R et al. (2012). Detection of Systemic Modification of Proteins in Mice by Sulforaphane after Oral Consumption.
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Ray R, Murdoch CE, Wang M et al. (2011). Endothelial Nox4 NADPH Oxidase Enhances Vasodilatation and Reduces Blood Pressure In Vivo.
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Charles RL, Burgoyne JR, Mayr M et al. (2011). Redox Regulation of Soluble Epoxide Hydrolase by 15-Deoxy-&Dgr;-Prostaglandin J2 Controls Coronary Hypoxic Vasodilation.
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Madhani M, Hall AR, Cuello F et al. (2010). Phospholemman Ser69 phosphorylation contributes to sildenafil-induced cardioprotection against reperfusion injury.
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Charles RL, Eaton P (2008). Redox signalling in cardiovascular disease.
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Burgoyne JR, Madhani M, Cuello F et al. (2007). Cysteine Redox Sensor in PKGIa Enables Oxidant-Induced Activation.
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Charles RL, Schröder E, May G et al. (2007). Protein Sulfenation as a Redox Sensor Proteomics Studies Using a Novel Biotinylated Dimedone Analogue*.
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Sponsors
Collaborators
Internal
- Prof Philip Eaton (WHRI)
- Dr Roberto Buccafusca (School of Physics and Chemical Sciences)
News
- Olive oil and salad combined 'explain' Med diet success (BBC News), May 2014
- Olive oil on salad may save your life (The Telegraph), May 2014