Gray Institute for Radiation Oncology and Biology is both a world class research centre for radiobiology and the leading facility in exploring the translational possibilities of this exciting field.
The Institute brings together researchers from around the world to the University of Oxford, into this newly created initiative within the Medical Sciences Division based at the Old Road Campus Research Building, Churchill Hospital, Oxford. Directed by Professor Gillies McKenna, the Institute is collaboratively supported by the Medical Research Council (MRC) and Cancer Research UK (CRUK).
The Institute further benefits from adjacencies to other research laboratories including the CR-UK funded Epidemiology Unit in the Richard Doll Building, the CR-UK funded Medical Oncology Unit at the Churchill Hospital, and the multidisciplinary Henry Wellcome Building for Genomic Medicine These, in addition to strong links with the Weatherall Institute for Molecular Medicine , Nuffield Department of Clinical laboratory Sciences and other departments within the University of Oxford, will provide an outstanding research and training environment for Radiation Oncology and Biology. With these considerable advantages ROB is already the premier Radiation Oncology and Biology research facility in the world.
We are particularly interested in working on ways to improve the ‘therapeutic ratio’ in radiation treatment. This ratio is the response of the tumour under radiation, to the damage to the normal tissues caused by radiation. It is decisive for how helpful radiation can be in treating tumours. We will focus on three areas of research, which have been identified by Professor McKenna as particularly ripe for clinical exploitation. These areas are:
DNA damage signalling
Understanding of the molecular biology of DNA damage and repair has expanded dramatically in the last five years. It is clear from studying naturally occurring mutations in the genes involved that such mutations result in very large alterations in radio sensitivity. These mutations thus represent targets worth exploring for therapeutic manipulation.
Study of DNA damage and repair is the largest and most comprehensive area in our current profile. Research into this area will be carried out by Peter O’Neill’s DNA Damage Group, Grigory Dianov’s Biochemistry Group, Tim Humphrey’s Cellular Responses Group, Thacker’s DNA Repair Group, Madalena Tarsounas’ group studying Recombinational DNA repair in telomere maintenance and Rothkamm’s group studying 'The role of H2AX in the mammalian DNA damage response'.
Differences in tumour versus normal tissue signal transduction
One of the ways in which cancerous tumour cells are different from the surrounding normal cells is that they display altered expression of signal transduction elements. The mutations caused by cancer affect processes such as proliferation, cell cycle checkpoints and escape from apoptosis. They may alter the radiation survival of cells, and are thus worth studying in order to improve the efficacy of radiotherapy.
Tumour microenvironment and its effects
In many ways, tumours differ biologically from the organs they affect. There are differences in vasculature, blood flow, interstitial pressure and oxygenation. These differences affect both how therapy can work, and how the tumours can progress. The work of several Radiation Oncology and Biology groups, including those of Professor Ruth Muschel, Professor Boris Vojnovic and Dr Eric Bernhard, involves investigation in this area.
These research areas will be supported by core facilities two core facilities:
Imaging is a key driving factor behind improvements in the field of radiation oncology. In the areas of tumour physiology, hypoxia and angiogenesis, imaging is critically important to assess strategies before they enter the clinic. Multiple groups will have interests in this area.
This facility will ensure the delivery of radiation sources for the centre, and also provide engineering support to calibrate and maintain the sources, and to assist with experimental work. Research in radiation physics will also help drive the development of radiation sources and techniques, and augment understanding of the biophysical processes underpinning the work of the Unit.
As part of the Radiobiology Initiative, clinical trials will be established. The senior clinical leaders of these trials will be Professor Gillies McKenna, Professor Ruth Muschel, Dr. Katherine Vallis and clinician scientists Dr Ricky Sharma and Dr Thomas Brunner. These trials will include:
Studies of signal transduction pathways in tumours
Professor McKenna has proposed trials with patients with head and neck, lung, pancreas or breast tumours. These trials will identify and test molecular targets for disruption of signal transduction pathways in tumours, to modify the ways tumours respond to either external beam irradiation or radio-labelled ligand therapy.
Studies of the protease inhibitor nelfinavir with radiation
These studies by will aim to improve the efficacy of radiation against tumours at a local level.
Development of radiopharmaceuticals for systemic use that target the cytotocicity of radiation directly to tumour cells
This work by Dr Katherine Vallis will have implications for the development of drugs that selectively deliver radiation to tumour cells.
The diagram below indicates how different areas will integrate. It envisages the Radiobiology Initiative as consisting of two major research areas: Basic (laboratory research) and Translational (moving from the laboratory to the clinic), supported by two core facilities (Radiation Biophysics and the Imaging Facility.) Some of the scientists fit clearly into one group or another (O’Neill, Dianov, Humphrey, Tarsounas and Rothkamm in Basic Research, and McKenna and Vallis in Translational). Others (Wardman, Bernhard, Muschel and Vojnovic) bridge areas.
The Gray Institute for Radiation Oncology and Biology initiative will:
The Old Road Campus Research Building (ORCRB) also houses the Structural Genomics Consortium, Jenner Institute, The Ludwig Institute, Clinical Pharmacology, the Institute of Biomedical Engineering together with the Knowledge Centre (part of University of Oxford Library Services, UNLS). We will work alongside other experts in the field, providing excellent opportunities for collaborations with other cancer related groups.