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David R. Bell

Publications Theses from Ph.D. students in the lab

Biography

After a degree in Biochemistry with Toxicology at the University of Surrey, I undertook a PhD in the molecular biology of cytochrome P450 at the University of London, joint between University College London and St. Bartholomews Hospital Medical College. I then went to ICI Central Toxicology Laboratory in Cheshire, to work with Dr Cliff Elcombe on the induction of cytochrome P450 CYP4A in peroxisome proliferation for three years. I then joined the Department of Zoology at Nottingham in January 1991, now the School of Biology. I spent a year on sabbatical (06/99-09/00) with Dr Alan Poland, at CDC/NIOSH in West Virginia, USA. My academic research in toxicology was leavened by service on the Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment and the European Food Safety Authority's Panel on food contact materials, enzymes, flavourings and processing aids. I also served on the British Toxicology Society's Executive Committee, and with the Eurotox Molecular Toxicology section. I left the University of Nottingham in 2009, to join the European Chemicals Agency.

Current Research Interests

I have a keen interest in the molecular mechanisms whereby toxins cause their various effects. The more poisonous it is, the more interesting is the basic component of the cellular machinery which it perturbs!

• Dioxin Toxicology

  2,3,7,8-tetrachlorodibenzo(p)dioxin is a representative of a class of non-genotoxic carcinogens which cause a programme of gene induction (eg cytochrome P450 CYP1A) through the Ah Receptor (Aryl hydrocarbon receptor). We are interested in fundamental studies on how the AhR is activated by agonists [1] [2] [3], and more applied studies in the risk assessment of dioxin and the implications for human health [4, 5, 6, 7].

• Liver Growth and Cancer

  The peroxisome proliferators and other non-genotoxic liver carcinogens cause a programme of gene induction (eg cytochrome P450 CYP4A) which leads to liver growth and tumorigenesis. We are interested in seeing how this occurs, and what leads to the remarkable coordination of cell growth and death in the liver [8] and other organs [9].

• Induction and Structure of Cytochrome P450

  Several chemicals induce specific cytochrome P450s, such as CYP4A, CYP2B or CYP1A. The cytochromes P450 are important in drug metabolism, but our understanding of these enzymes is limited because we do not know their structure, and how this structure changes during catalysis. We have cloned novel human and mouse cytochromes P450 [10, 11], and are interested in determining their structure and function.

• C. elegans As A Model System For Studying Toxins

  C. elegans is a simple, but well characterised, organism, with full genome sequence available. We have been able to use this organism to study the mechanism of action of Black Widow Spider venom, and its receptor, latrophilin [12]. We have been able to extend these studies to find out more about the receptor, and about the mechanism of action of other drugs and chemicals [13].

Updated on: 02/12/2009