Our research team aims to develop humanised biologically-relevant models to improve our ability to predict the safety of drugs in development, and those that are widely-used in patients but which possess some safety liability. In parallel we work on improving biomarkers that can allow a better definition of the safe use of medicines. The overarching goal of our research is to improve our understanding of adverse drug reactions from a human health perspective; therefore, we have established national and international links with academic scientists, clinicians and colleagues in the pharmaceutical industry, to ensure our work is relevant to patients and the process of drug development.
We have spent many years attempting to improve models of the human liver, and also other organs, for example leading the recent UKRI 3Dbionet project to enhance uptake of 3D in vitro models. Our philosophy in this endeavour is based on George Box’s famous aphorism, “All models are wrong, but some are useful" - we try to understand what is actually pharmacologically-relevant in a given model. Working with clinical colleagues, and through the kind agreement of many patients, we established a pipeline for the use of human primary liver cells (>380 freshly-isolated archived liver tissue and cell culture since 2011), this allowed the evaluation of 3D models of the liver using patient-derived tissue, as well as creating a bank of patient-derived induced pluripotent stem cells. We led an industry-academic consortium to evaluate the reproducibility of such in vitro models – an absolute priority for industry drug development - and an examination of the physiological relevance of such liver models, largely through a proteomic approach. Alongside twelve industry partners, this led to the development of a roadmap, accepted by and now being used by a number of European Pharmaceutical companies, for the adoption of different models for the safety assessment of pharmaceutical compounds. Through further Innovative Medicines Initiative funding we led an evaluation of the role of systems toxicology models in drug safety assessment, which will now be developed into a new published roadmap.