Dr Dean Willis
Inflammation is normally a protective response which is vital to the continuing well being of complex organisms. It is initiated in response to an invasion of the host by pathogens, mechanical trauma, toxins or neoplasm and attempts to destroy, dilute or wall-off the inflammatory stimuli or damaged host tissue. The inflammatory response itself involves the interaction of vasculature and cellular processes which are themselves controlled by a myriad of biological mediators. An insufficient inflammatory response renders the individual susceptible to opportunistic infection while an excessive/inappropriate inflammatory response leads to chronic inflammatory diseases such as rheumatoid arthritis and multiple sclerosis. The main aim of our research is to understand the mechanisms which underlie the transition from resolving "physiological" inflammation to chronic "pathological" inflammation. In particular we are focusing on the dynamics of inflammation and the identification of points of fragility in this response, which when perturbed, could lead to a persistent/excessive inflammation. Specific research projects in our laboratory are, 1) Chronic Granulomatose Disease (CGD) has model to discovering the dynamics and controls points in resolving and non-resolving inflammatory responses. (This in vivo platform is also being developed for drug discovery, allowing the effect of potential drug candidates on physiological and pathophysiological inflammation to be compared). 2) The Heme oxygenase system as a Hub for the convergence of oxidative stress, infection/inflammation and metabolism. 3) Macrophage heterogeneity has a design principal for an efficient inflammatory response. 4) The design of an in vitro dynamic model of human inflammation. (This is a unique model designed to study the dynamics of human inflammation and aid drug discovery). 5) In silco modeling/simulation of inflammation. The underlying philosophy behind our research is that the quantitative modeling of physiological and pathophysiological inflammation can be leveraged against the innate complexity of the response when attempting to identify critical inflammatory pathways and drug targets. It is hoped that this research will help establish a toolbox of methodologies in which the relative contribution of differing pathways/mediators to an inflammatory response and the therapeutic potential of different anti-inflammatory targets can be quantified and prioritized. In addition I am interested in the Translation of academic research into commercial opportunities (technology evaluation, patent application and Business plan development) and in this respect I act as an Business fellow for the London technology Network.
Course organiser PHAR3005 (Immunopharmacology 1 unit),Course organiser PHAR3031 (Immunopharmacology 0.5 unit), Industrial Placement Tutor, Affilate Student Tutor (Pharmacology)
- Atzori L, Chua F, Dunsmore SE, Willis D, Barbarisi M, McAnulty RJ, Laurent GJ (2004). Attenuation of bleomycin induced pulmonary fibrosis in mice using the heme oxygenase inhibitor Zn-deuteroporphyrin IX-2,4-bisethylene glycol.. Thorax, 59(3), 217 - 223.
- Wagener FA, Volk HD, Willis D, Abraham NG, Soares MP, Adema GJ, Figdor CG (2003). Different faces of the heme-heme oxygenase system in inflammation. Pharmacological Reviews, 55(3), 551 - 571. doi:10.1124/pr.55.3.5
- Braudeau C, Bouchet D, Toquet C, Tesson L, Menoret S, Iyer S, Laboisse C, Willis D, Jarry A, Buelow R, Anegon I, Chauveau C (2003). Generation of heme oxygenase-1-trnasgenic rats. Bulletin of Experimental Biology and Medicine, 228(5), 466 - 471.
- Jenkins RG, Meng QH, Hodges RJ, Lee LK, Bottoms SE, Laurent GJ, Willis D, Ayazi Shamlou P, McAnulty RJ, Hart SL (2003). Formation of LID vector complexes in water alters physicochemical properties and enhances pulmonary gene expression in vivo.. Gene Therapy, 10(12), 1026 - 1034. doi:10.1038/sj.gt.3301963
- Horvath I, MacNee W, Kelly FJ, Dekhuijzen PN, Phillips M, Doring G, Choi AM, Yamaya M, Bach FH, Willis D, Donnelly LE, Chung KF, Barnes PJ (2001). Haemoxygenase-1 induction and exhaled markers of oxidative stress in lung diseases. European Respiratory Journal, 18(2), 420 - 430.
- Paul-Clark MJ, Gilroy DW, Willis D, Willoughby DA, Tomlinson A (2001). Nitric oxide synthase inhibitors have opposite effects on acute inflammation depending on their route of administration. The Journal of Immunology, 166(2), 1169 - 1177.
- Willis D, Moore AR, Willoughby DA (2000). Heme oxygenase isoform expression in cellular and antibody-mediated models of acute inflammation in the rat.. J Pathol, 190(5), 627 - 634. doi:10.1002/(SICI)1096-9896(200004)190:5<627::AID-PATH556>3.0.CO;2-2
- Seed MP, Gilroy DW, Paul-Clark MJ, Colville-Nash PR, Willis D, Tomlinson A, Willoughby DA (1999). Role of inducible enzymes cyclooxygenase-2, nitric oxide synthase and heme oxygenase in angiogenesis of inflammation. In Willoughby DA, Tomlinson A (Ed.), Inducible Enzymes in the Inflammatory Response (pp. - ). : Birkauser Verlag.
- Gilroy DW, Colville-Nash PR, Willis D, Chivers J, Paul-Clark MJ, Willoughby DA (1999). Inducible cyclooxygenase may have anti-inflammatory properties. Nature Medicine, 5(6), 698 - 701.
- Willis D (1999). Overview of HO-1 in inflammatory pathologies. In Willoughby DA, Tomlinson A (Ed.), Inducible Enzymes in the Inflammatory Response (pp. 55 - 92). : Birkauser Verlag.
- Willis D (). Persistent inflammation in mouse chronic granulomatous disease is reversed by heme oxygenase-1 inducers.. Journal of Immunology, , - .
- Assari T, Willis D (). Translocator Protein (TSPO-18) regulates inflammasomme activation in human macrophages: A link to Chronic Granulomatous Disease. Journal of Leukocyte Biology, , - .
- Peh KH, Willis D (). Carbon Monoxide is a Chemoreppellent: A novel mechanism of action in inflammation.. Blood, , - .
- Willis D (). Sex differences and anti-inflammatory drugs effects on a model of sterile inflammation in chronic granulomatous disease (CGD) mice.. Journal of Inflammation, , - .