Dr Richard Hopkinson

Dr Richard Hopkinson

Lecturer of Organic Chemistry

Tel: 0116 252 5185

Email: richard.hopkinson@leicester.ac.uk

Personal details

Research

My research is focused on understanding how reactions between biomolecules and reactive small molecules, most notably formaldehyde, affect biological systems in health and disease.

Formaldehyde, the simplest aldehyde, is a highly-reactive electrophile with widespread uses in industry, including in plastics manufacturing, tanning, embalming, and cosmetics. Formaldehyde has long been considered a human health risk resulting in short-term and long-term health effects; acute exposure can induce nausea, inflammation, arrhythmia, convulsions, coma and renal failure, while chronic exposure is linked with numerous cancers and neurodegeneration. Recent studies have revealed that formaldehyde is a by-product of enzymatic demethylation reactions on chromatin. Therefore cells are constantly exposed to endogenously-produced formaldehyde, revealing the potential for formaldehyde to cause disease when its production and/or metabolism are dysregulated. It is also possible that cellular formaldehyde plays important regulatory and/or sensing roles.

I am interested in determining how formaldehyde’s reactions in cells regulate cell functions. The mechanisms underpinning formaldehyde toxicity are poorly understood, which is a consequence of its complex and uncharacterised reactivity with biomolecules, often involving unstable intermediates. My research uses chemical/synthetic, biochemical and cellular methods to (i) characterise the reactions of formaldehyde with biomolecules in vitro and in cells, (ii) identify functional/structural changes in biomolecules as a consequence of formaldehyde reactions, (iii) define the mechanisms of endogenous formaldehyde production and metabolism, (iv) detect and modulate cellular formaldehyde levels, and (v) correlate formaldehyde reactivity with functional changes in cells. Overall, the work seeks to identify mechanisms of formaldehyde toxicity that can be targeted for therapeutic benefit.

Scheme showing the sources and fates of cellular formaldehyde.

Selected Publications

  • Highly Selective Inhibition of Histone Demethylases by De Novo Macrocyclic Peptides A. Kawamura*, M. Münzel, T. Kojim, C. Yapp, A. Tumber, Y. Goto, T. Katoh, O. N. F. King, S. Müller, P. E. Brennan, R. Chowdhury, R. J. Hopkinson, H. Suga*, C. J. Schofield*, Nature Communications, 2017, 8, 14773.
  • Plant Cysteine Oxidases are Dioxygenases that Directly Enable Arginylation of N-End Rule Targets M. D. White, M. Klecker, R. J. Hopkinson, D. Weits, C. Mueller, C. Naumann, R. O’Neill, J. Wickens, T. Grossman, N. Dissmeyer*, E. Flashman*, Nature Communications, 2017, 8, 14690.
  • Arginine demethylation is catalysed by a subset of JmjC histone lysine demethylases L. J. Walport, R. J. Hopkinson, W. Ge, R. Chowdhury, A. Kawamura, C. J. Schofield*, Nature Communications, 2016, 7, 11974.
  • Analysis of JmjC Demethylase-Catalysed Demethylation using Geometrically-Constrained Lysine Analogues G. W. Langley, A. Brinkø, M. Münzel, L. J. Walport, C. J. Schofield*, R. J. Hopkinson* ACS Chemical Biology, 2016, 11 (3), 755–762.
  • Studies on Glutathione-Dependent Formaldehyde-Activating Enzyme from Paracoccus denitrificans R. J. Hopkinson*, I. K. H. Leung, T. J. Smart, N. R. Rose, L. Henry, T. D. W. Claridge, C. J. Schofield* PLOS ONE, 2015, DOI: 10.1371/journal.pone.0145085.
  • Is JmjC Oxygenase Catalysis Limited to Demethylation? R. J. Hopkinson, L. J. Walport, M. Münzel, N. R. Rose, T. J. Smart, A. Kawamura, T. D. W. Claridge, C. J. Schofield*, Angewandte Chemie International Edition 2013, 52, 7707-7713.
  • Studies on the reaction of glutathione and formaldehyde using NMR R. J. Hopkinson, P. S. Barlow, C. J. Schofield*, T. D. W. Claridge*, Organic and Biomolecular Chemistry 2010, 8, 4915-4920.
  • Monitoring the activity of 2-oxoglutarate dependent histone demethylases by NMR spectroscopy: Direct observation of formaldehyde R. J. Hopkinson, R. B. Hamed, N. R. Rose, T. D. W. Claridge, C. J. Schofield*, ChemBioChem. 2010, 11, 506-510.

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Contact Details

Department of Chemistry
University of Leicester
Leicester, LE1 7RH, UK

Email: chemistry@le.ac.uk

Tel: [+44] (0)116 252 2100

Fax: [+44] (0)116 252 3789

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