Jonathan Coulter

Dr Jonathan Coulter joined the School of Pharmacy in June 2012, with a central research theme of developing novel therapeutics to increase tumour cell radiation sensitivity. This stems from the fact that at least 75% of all cancer patients receive radiotherapy as part of their treatment, with almost 60% of those patients treated with curative intent. The development of novel radiosensitising strategies has the potential to markedly improve these statistics while concurrently reducing dose-limiting toxicity to surrounding healthy tissue.

One key research strand involves the characterisation of gold nanoparticles as novel radiosensitising agents that exhibit a low toxicity potential. These desirable properties are tempered by the fact that clinically unfeasible concentrations of gold are required to generate significant radiosensitation. To address this, Jonathan’s group, in collaboration with Dr Dorian Dixon at the Nanotechnology and Integrated BioEngineering Centre (University of Ulster), have developed co-functionalised gold nanoparticles that prevent agglomeration under physiological conditions, while simultaneously promoting nanoparticle internalisation. Using this strategy, we have reduced the radiosensitising concentration of gold nanoparticles 20-fold, and have elucidated key biological mechanisms underpinning their efficacy.

Jonathan was recently awarded Prostate Cancer UK funding to develop a second-generation gold nanoparticle based on this technology. In this 13 project, ionising radiation will be utilised both as a primer (low dose) to induce specific expression of a target receptor on prostate tumor cells, and in a therapeutic context post nanoparticle exposure. Gold nanoparticles will be co-functionalised with stabilising polymers and biologically active, antagonistic pepducins known to inhibit activation of the PI3K/Akt pro-survival pathway. Jonathan anticipates that this approach will provide a tumour-targeting strategy, while providing both physical and molecular approaches to augment radiation sensitivity.

In a separate project, Jonathan’s team are supporting data acquisition for the MEDIC network consortium on an EPSRC funded project entitled: “Improving patient outcome by integrating the generic with the personal”. This multi-centre project involving University of Cranfield, Imperial College London, University of Nottingham, University of Stirling and Queens’ University aims to determine the potential of radiation/drug/nanoparticle interactions using predictive mathematical models of combination therapies, validated alongside experimentally derived measurements. This is being developed in the first instance using glioblastoma as the treatment exemplar, with the long-term objective of establishing a generic modelling framework adaptable to a range of tumours and combined therapies.

Recently, Jonathan has developed an interest in the contribution of cancer stem cell-mediated radioresistance and treatment failure. Specifically, he aims to develop gold nanoparticles targeted to these sub-populations using an anti-angiogenic and anti-stem cell peptide, ALM201, that targets this population of cells. This was developed by Professor Tracy Robson from the School of Pharmacy, and is now in phase I/II clinical trials. Although at an early stage this work is supported by collaborations with world leading experts including Professor Robert Bristow (University Health Network, Toronto) and Professor Norman Maitland (York Cancer Research Unit).

 Jonathan has published widely on subjects including nanoparticle and gene therapy radiosensitisation, given invited presentations at conferences and seminars both nationally and internationally, and has been supported by funding from the EPSRC, Cancer Research UK and Prostate Cancer UK.

RESEARCH PARTNERS

• Prostate Cancer UK
• Engineering and Physical Sciences Research Council
• University College Dublin
• Ulster University
• University Health Network – Ontario Cancer Institute
• Cancer Research UK
• The University of York