|
|
|
Dr Wendy-Anne Smith
Division of Molecular Biotechnology, TVW Telethon Institute for Child Health Reasearch and Centre for Child Health Research
University of Western Australia
PO Box 855, West Perth, 6872
Email: wendy@ichr.uwa.edu.au
Tel: +61-8-9489 7870
Fax: +61-8-94897700
Homepage:
| Research |
| Our research concentrates on the molecules that cause allergic sensitisation and the development of immunotherapy to prevent and treat allergic diseases, especially asthma. A large focus of our work has been with house dust mite allergens and we have cloned and synthesized recombinant allergens corresponding to most of the 19 HDM allergens currently identified. Five of these 19 allergenic proteins are proteases, group 1 (cysteine), group 3 (trypsin), group 6 (chymotrypsin) and the group 9 (collagenolytic serine protease; identified by G. Stewart) proteins. The corresponding natural protein for all these allergens has been isolated and shown to have the relevant protease activity (work done by ourselves and others in the field). The structural information and the production of high levels of highly purified recombinant proteases are being obtained principally to develop new types of immunotherapy (IT). One of the ways in which we study the role of these protease allergens in causing the initial sensitization and modulation of the immune responses observed in allergic diseases, is to use the recombinant proteins to measure IgE reactivity, T cell proliferation and cytokine production in human sera and peripheral blood mononuclear cells. In another aspect of our work looking specifically at experimental sensitization and IT we have developed a mouse asthma model. We found that intranasal administration of a cysteine protease homologue of the group 1 allergen induced prolonged and boostable IgE responses. Upon challenge the mice also produced a lymphocytic and eosinophilic lung infiltrate and Th2 cytokines. Enzymatic activity wasn?t absolutely required for sensitization but could under some circumstances be stimulatory or inhibitory. In general, the role of the protease activity in these allergens remains unclear. |
|
| Collaborations |
Prof David Kemp (QIMR)
ALK-Abello Pharmaceuticals (Denmark)
|
|
| Publications |
Thomas WR, Smith W, Hales BJ, Mills KL and O'Brien RM. (2002) Characterization and immunobiology of house dust mite allergens. Int Arch Allergy Immunol; 129:1-18.
Smith WA, Chua KY, Kuo MC, Rogers BL, Thomas WR. (1994) Cloning and sequencing of the Dermatophagoides pteronyssinus group III allergen, Der p III. Clin Exp Allergy; 24(3): 220-228.
Smith WA, Hales BJ, Jarnicki AG, Thomas WR. (2001) Allergens of wild house dust mites: environmental Der p 1 and Der p 2 sequence polymorphisms. J Allergy Clin immunol; 107(6): 985-992.
Jarnicki, AG and Thomas, WR. (2002) Stimulatory and inhibitory epitopes in the T cell responses of mice to Der p 1. Clin Exp Allergy; 32(6): 942-950.
|
|
|
|
|
|
|
|
|
