Henderson

Biography

Colin Henderson received his BSc (Hons) (1981) in Biochemistry and PhD (1985) from the Medical Faculty, both University of Edinburgh. First postdoctoral position with the MRC Reproductive Biology Unit in Edinburgh (1984-1987); joined group of Roland Wolf (1987) at Imperial Cancer Research Fund (later Cancer Research UK) at the University of Edinburgh. Relocated as Chief Scientific Officer with Cancer Research UK group to Biomedical Research Centre, University of Dundee in 1993; became Staff Scientist with Cancer Research UK group (1999). Honorary Senior Lecturer in the Biomedical Research Centre (2000); appointed as Senior Lecturer at the University of Dundee in Division of Cancer Research, Medical Research Institute in April 2011.

Research Interest

Transgenic technology has the potential to revolutionise the fields of toxicology and drug metabolism; the ability to manipulate genetically the expression of individual drug metabolising enzymes in order to better understand their function(s) could lead to the development of new drugs for the treatment of diseases such as cancer, as well as the optimisation of treatment regimes with existing drugs. I have worked in this area for nearly 20 years, developing a number of transgenic mouse models to facilitate the study of how drug metabolising enzymes protect us from the chemically challenging environment in which we live, and how the expression of these enzymes is related to the aetiology of cancer. My current research interests centre around the post-translational modification of proteins on cysteine residues by addition of the abundant cellular thiol glutathione, and the involvement of glutathione transferase P (GSTP) in this process. GSTP is expressed at elevated levels in a number of animal and human tumours, and in cell lines made resistant to a variety of drugs. Little, however, is known about the endogenous role(s) of this enzyme. We were the first to describe deletion of GSTP in mice, which are apparently phenotypically normal, although they display an increased resistance to acetaminophen involving a mechanism(s) which have not yet been fully elucidated, but which may involve GSTP acting as an inhibitor of Jun kinase, thus effecting cellular signalling cascades and the regulation of stress response genes. GSTP null mice also have significantly higher levels of tumour formation in the skin or lungs, when challenged chemically, or in the colon in a genetic model (APCMin). Gene expression profiling suggests a role for GSTP in regulating innate immunity and inflammatory processes, which is the subject of ongoing investigation. More than 100 proteins have been shown to be glutathionylated, including several involved in energy metabolism and the cytoskeleton. However, the extent to which proteins are glutathionylated/deglutathionylated, under what circumstances and the physiological significance, remains to be determined. My research will use a variety of in vitro and in vivo approaches, including cell lines and transgenic mice, to investigate and characterise the ‘glutathiome’ and the cellular consequences arising from these protein modifications. I am also involved in an EU-funded Innovative Medicines Initiative (MARCAR - Markers of Carcinogenesis) in which transgenic reporter mouse lines are used to investigate the relationship between oxidative stress and non-genotoxic carcinogenesis, with a view to identifying early biomarkers. This is a collaboration between academic centres and pharmaceutical partners across Europe. I am a co-grant holder (with Professor Roland Wolf) in an ERC Advanced Investigator award (REDOX) looking at the role of oxidative stress in disease aetiology and development of new methods of detecting oxidative stress, including non-invasive in vivo systems.