Ian Copple

Professor of Pharmacology & Toxicology, University of Liverpool

Ian Copple is Professor of Pharmacology & Toxicology and currently holds a 5-year Senior Nonclinical Fellowship from the UK Medical Research Council. Ian leads the Stress Response Lab (www.liverpool.ac.uk/stress-response-lab), a group of 8 pre/post-doctoral researchers interested in pharmacological and toxicological aspects of stress response pathways, and particularly the NRF2 oxidative stress response. He is also academic lead of the Human Liver Research Facility in Liverpool (www.liverpool.ac.uk/hlrf). He works extensively with the pharmaceutical industry and has participated in several EU Innovative Medicines Initiative academic-industry research programs. Ian has received several awards for his research from national and international societies, including the 2023 Early Career Toxicology Award from the American Society of Pharmacology & Experimental Therapeutics (ASPET) and the 2018 Early Career Investigator Prize from the British Toxicology Society. He is also a Fellow of the British Pharmacological Society and the current Chair of the Scientific Subcommittee of the British Toxicology Society.

Presentation: Pharmacology and toxicology of cellular stress responses – progress and challenges

Mammalian cells are equipped with several biochemical pathways that enable the sensing of a range of endogenous and exogenous stresses and mediate appropriate adaptive responses. For example, these pathways govern cellular responses to protein misfolding, hypoxia and DNA damage. As a demonstration of the bridge between toxicology and pharmacology, these stress response pathways are attracting interest as novel therapeutic targets in numerous pathologies. A leading example is the transcription factor NRF2, which protects mammalian cells against chemical and oxidative stress. The activation of NRF2 signalling has been used as an indicator of a risk of drug-induced toxicity. Conversely, a small number of NRF2 activating drugs have been approved as medicines so far, and several pharmaceutical companies have ongoing NRF2 activator drug development programs. Recent advances in the therapeutic targeting of NRF2 are accompanied by numerous challenges. These include short and long-term safety considerations of pharmacologically stimulating the NRF2 pathway, understanding the human relevance of the pre-clinical species that are routinely used in the drug development process, and the absence of robust methods for monitoring target engagement and pharmacodynamic responses in the clinic. In this presentation, I will describe efforts to address these challenges through a range of non-clinical and clinical studies. The goal of this work is to support the development and use of NRF2 activators as novel therapies across a range of diseases. 

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