Christopher J. Schofield

Christopher Joseph Schofield (also known as Chris Schofield) is the Head of Organic Chemistry at the University of Oxford and a Fellow of the Royal Society. Chris Schofield is a professor of organic chemistry at the University of Oxford, Department of Chemistry and a Fellow of Hertford College. Prof Schofield is an international leader in functional, structural and mechanistic understanding of enzymes that employ oxygen and 2-oxoglutarate as a co-substrate. His work has opened up new fields in antibiotic research, oxygen sensing, and gene regulation.
After groundbreaking work on plant and microbial oxygenases, he pioneered structurally informed functional assignments for uncharacterised human oxygenases. His research has identified unanticipated roles for oxygenases in regulating gene expression, importantly in the cellular hypoxic response, and has revealed new post-translational modifications to chromatin and RNA splicing proteins. The work has identified new opportunities for medicinal intervention that are being pursued by numerous academic and commercial laboratories.

Chris Schofield studied for a Bachelor of Science in chemistry at the University of Manchester and graduated with a first class honour (1979-1982). In 1982, he moved to Oxford to study for a DPhil with Professor Jack E. Baldwin. In 1985, he became a Departmental Demonstrator in the Dyson Perrins Laboratory, Oxford University followed by his appointment as a Lecturer in Chemistry and a Fellow of Hertford College in 1990. In 1998, he became Professor of Chemistry, and in 2011 he was appointed the Head of Organic Chemistry at the Department of Chemistry, University of Oxford. In 2013, he was elected a Fellow of the Royal Society, FRS.

Chris Schofield runs a laboratory of undergraduate Part-II, Master, and DPhil students, visiting researchers, post-doctoral research assistants, and staff members. His laboratory members have received scholarships and funding from the British Heart Foundation, the BBSRC, the Wellcome Trust, the Biochemical Society, Cancer Research UK, and other funding bodies. The work in the laboratory focuses on different areas of research, including:

Molecular Mechanisms of the Hypoxic Response

Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric α,β-transcriptional complex that mediates the cellular response to oxygen availability in multicellular organisms, ranging from the simplest known animal Trichoplax adhaerens to humans. Investigating the structures and mechanisms of the HIF prolyl hydroxylases is a current focus of the work. The group solved crystal structures of PHD2 - one of the human prolyl hydroxylases and discovered that the HIF asparaginyl hydroxylase also catalyses hydroxylation of conserved motifs, the ankyrin repeat domain.

Chemical Basis of Epigenetics

A current focus of the group is modification of histones, in particular oxygenase catalysed N-demethylation of histone methylated-lysine residues – in collaboration with the Structural Genomics Consortium. The histone demethylases are of interest both with respect to their links to diseases, including cancer and inflammatory diseases, as well as the role of methylation in transcriptional regulation. Recent areas of interest include the fat mass and obesity protein which was shown to be a nucleic acid demethylase and JMJD6 which is a lysyl hydroxylase modifying RNA splicing protein.

Structural and Functional Studies on 2OG Oxygenases

The 2-oxoglutarate (2OG) dependent oxygenases are a superfamily of non-haem iron dependent oxygenases, most of which use the Krebs cycle intermediate, 2-oxoglutarate (2OG), as a cosubstrate. The group are interested in understanding these enzymes for their ability to catalyse synthetically difficult or ‘impossible’ reactions (e.g. the stereoselective hydroxylation of unactivated carbon-hydrogen bonds), for their diverse physiological roles, and for their links to disease. The research focuses on members of the family that are linked to disease, or can be targeted for the treatment of disease. Techniques involved in this interdisciplinary research include proteomics, X-ray crystallography, biological mass spectrometry, molecular biology, enzyme kinetics and organic synthesis/medicinal chemistry.

Antibiotics: Biosynthesis and Resistance Mechanisms

Most clinically used antibiotics are based upon natural products. The most important family of antibiotics contains a β-lactam ring, and includes the penicillin, cephalosporin, clavam, and carbapenem antibiotics. The group's biosynthetic work has focused on the clavams and carbapenems, with a particular focus being on the mechanism and structures of enzymes that catalyse chemically 'interesting' steps. The biggest threat to the continued use of β-lactam antibiotics is that of bacterial resistance. Prof Schofield is currently working on the design and synthesis of enzyme inhibitors for the metallo β-lactamases – there are no clinically used inhibitor of these enzymes but they pose a significant threat as they catalyse the hydrolysis of almost all clinically used β-lactam antibiotics. A particular interest involves human metallo β-lactamases which share the same fold

Prof Schofield was elected a Fellow of the Royal Society in 2013.