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Cancer

"The University of Oxford, already a world leader in many aspects of cancer research, has recently identified cancer as a major strategic priority and has begun to co-ordinate its research activities in the area, particularly with regard to translational research."
The University of Oxford, already a world leader in many aspects of cancer research, has identified cancer as a major strategic priority and begun to co-ordinate its research activities in the area, particularly with regard to translational research. This has been reinforced by the establishment of the Oxford Cancer Research Centre (www.cancercentre.ox.ac.uk) and the University Department of Oncology (www.oncology.ox.ac.uk).

Research embraces Oxford’s traditional and continued strengths in preclinical sciences, and couples these with rapidly expanding clinical and translational research activity. One of the key aims will be the optimal translation of fundamental research into patient benefit and for Oxford to become the leading centre for translational early-phase oncology trials in the UK.

Further details of Oxford cancer activity, including profiles of individual researchers, can be found at
www.cancercentre.ox.ac.uk, the website for the Oxford Cancer Research Centre. For specific queries, please contact Dr Claire Bloomfield, the OCRC Project Manager: claire.bloomfield@oncology.ox.ac.uk.

Current Projects Include:

Professor Steve Davies and Dr Angela Russell

Oxford Chemistry Department has a proven track record for translational research in the field of small molecule drug discovery in cancer and there is a drive to progress this area of research through collaboration, but activities are currently limited by a lack of resource in synthetic chemistry. The CRUK Small Molecule Cancer Drug Discovery programme will supply seed-corn funding for a team of medicinal chemists to provide critical mass to drive a series of co-ordinated programmes in cancer drug discovery in Oxford.

Molecular interactions within the hypoxia sensing and response system
Protein Arginine Methyltransferases (PRMTs)
Serine/Threonine Protein Kinases
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Professor Chris Schofield

A particular focus of the Schofield group has been the oxygen dependent regulation of the transcription factor hypoxia inducible factor (HIF) (in collaboration with Peter Ratcliffe and Chris Pugh). HIF is a master regulator of the transcriptional response to limiting oxygen concentrations in metazoan cells and controls the production of proteins such as erythropoietin (EPO) and vascular endothelial growth factor (VEGF) that work to supply cells with oxygen. The levels and activity of the α-subunit of HIF are regulated by its post-translational hydroxylation, and the oxygen dependent HIF hydroxylases effectively act as oxygen sensors. They are interested in understanding the chemical and structural basis by which the HIF hydroxylases enable the hypoxic response. They aim to inspire the development of new treatments that employ modifications of HIF hydroxylase activity, including by inhibition with small molecules. Modulation of the HIF mediated hypoxic response is of potential use in a wide range of disease states including cancer and cardiovascular disease.
Epigenetics

A current focus is modification of histones, in particular oxygenase catalysed N-demethylation of histone methylated-lysine residues - in collaboration with the Structural Genomics Consortium (SGC). 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. We are also interested in the identifying other oxygen dependent interfaces in the regulation of gene expression, particularly those that have pathophysiological relevance. Recent areas of interest include the fat mass and obesity protein which we have shown to be a nucleic acid demethylase and JMJD6 which is a lysyl hydroxylase modifying RNA splicing protein.

In collaboration with the SGC and industrial partners (including GlaxoSmithKline and Pfizer), we are developing small-molecule 'probes' for histone modifying and binding proteins. The current focus in our group is on enzymes from the JmjC family of histone demethylases.