Immunopharmacology of inflammation
Dr Dean Willis
|Lecturer Tel: 020 7679 3755|
Dr Dean Willis graduated in Biochemistry before taking his PhD (1997) in Pathology/Pharmacology at the William Harvey Research Institute, St Bartholomew’s Medical School. He stayed on at the William Harvey holding an Oliver-Bird Fellowship in Rheumatic Diseases. In 1999 he was appointed a lecturer in the Department of Pharmacology, UCL.
Inflammation is normally a protective response which is vital to the continuing well being of complex organisms. It is initiated in response to invasion of the host by pathogens, mechanical trauma, toxins or neoplasms and attempts to destroy, dilute or wall-off the inflammatory stimuli or damaged host tissue. The inflammatory response itself involves a complex interaction of vasculature and cellular processes which is controlled by a myriad of biological mediators. An insufficient inflammatory response renders the individual susceptible to opportunistic infection and tumour development while an excessive inflammatory response leads to chronic inflammatory diseases such as rheumatoid arthritis and multiple sclerosis.
The main focus of our research is to elucidate inflammatory cascades using in vitro and in vivo models. In particular we are focusing on molecular mechanisms, which contribute to the down regulation of inflammatory reaction and the resolution of inflammatory lesions. By using novel models of resolving and non-resolving inflammation and current micro-array techniques it is hoped that important regulatory events in the inflammatory response can be identified. These targets are then validated by the use of transgenics or the recently elucidated siRNA technology. Three specific areas are currently being investigated.
- The role of Heme oxygenase in inflammation. Heme oxygenase is the rate limiting enzyme in the catabolism of heme and which we have previously demonstrated to regulate the resolution of inflammatory lesions. The role of Heme oxygenase in regulating leukocyte activation is currently being studied
- Chronic Granulomatous diseases as a model for elucidating anti-inflammatory pathways. CGD is a disease in which the enzyme NADPH oxidase becomes inactive in leukocytes. As well as contributing to anti-microbial activity we have demonstrated that NADPH oxidase regulates endogenous anti-inflammatory cascades. Research is currently focused on elucidating this novel action of NADPH oxidase.
- Macrophage biosynthetic pathways and there control of inflammatory mediator release. Inflammation requires a significant increase in the production of biological mediators by cells. We are investigating if macrophages process specific biosynthetic pathways for the generation of these biologics and if these could be a viable drug target.
Current research collaborations include Institute of Child Health, William Harvey Research Institute, Humboldt-Universitaet Berlin, University of Erlangen, Fleming Institute Athens, University of Nijmegen, Institute Gulbenkian de Cienca, Harvard Medical School, Centre Hospitalier University de Nantes and Imtix-SangStat.
Recent and selected papers
- Jenkins RG, Meng QH, Hodges RJ, Lee LK, Bottoms SE, Laurent GJ, Willis D, Ayazi Shamlou P, McAnulty RJ, Hart SL.Formation of LID vector complexes in water alters physicochemical properties and enhances pulmonary gene expression in vivo. Gene Ther. 2003;10:1026-34
- Braudeau C, Bouchet D, Toquet C, Tesson L, Menoret S, Iyer S, Laboisse C, Willis D, Jarry A, Buelow R, Anegon I, Chauveau C. Generation of heme oxygenase-1-transgenic rats. Exp Biol Med. 2003;228:466-71.
- Willis D, Moore AR, Willoughby DA. Heme oxygenase isoform expression in cellular and antibody-mediated models of acute inflammation in the rat. J Pathol. 2000;190:627-34
- Gilroy DW, Colville-Nash PR, Willis D, Chivers J, Paul-Clark MJ, Willoughby DA. Inducible cyclooxygenase may have anti-inflammatory properties. Nat Med. 1999;5:698-701
- Willis D, Moore AR, Frederick R, Willoughby DA. Heme oxygenase: a novel target for the modulation of the inflammatory response. Nat Med. 1996;2:87-90.