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Dr Dianne J Watters
Eskitis Institute for Cell and Molecular Therapies and School of Biomolecular and Biomedical Science
Griffith University
Nathan Campus, Brisbane, Queensland 4111
Email: D.Watters@griffith.edu.au
Tel: +61-7-3875 7383
Fax: +61-7-3875 7656

Our interests are in the molecular mechanisms of apoptosis (programmed cell death) and how tumour cells avoid death induced by radiation or chemotherapeutic drugs. The major effectors of the apoptosis programme are cysteine proteases, which cleave after aspartic acid (caspases). Caspase activation occurs through two major pathways: one emanating from death receptors (such as Fas) leading to activation of the apical caspase-8 and the other involving the mitochondrion with activation of apical caspase-9 by released cytochrome C. Apoptosis in response to ionizing radiation is thought to involve activation of the tumour suppressor p53 and subsequently the mitochondrial pathway. In a tumour line which has mutant p53 and lacks surface Fas receptors we have evidence for the involvement of caspase-8 in the initiation of ionizing radiation (IR)-induced apoptosis. We are interested in investigating this novel pathway, and determining how caspase-8 is activated after IR. These studies may lead to the development of therapeutic targets to induce apoptosis in tumour cells and will lead to a greater understanding of how tumour cells can evade apoptosis and hence become resistant to therapy.
Professor Martin Lavin, QIMR.
Professor David Fairlie, IMB, UQ.
Waterhouse, N., Kumar, S., Strike, P., Sparrow, L., Song Q, Dreyfuss, G., Alnemri E., Litwack G., Lavin, M.F. and Watters, D. (1996) Heteronuclear ribonucleoproteins C1 and C2, components of the spliceosome, are specific targets of ICE-like proteases in apoptosis. J. Biol. Chem. 271, 29335-29341.

Harvey, K.F., Harvey, N.L., Michael, J.M., Parasivam, G., Waterhouse, N., Alnemri, E.S., Watters, D. and Kumar, S. (1998) Caspase-mediated Cleavage of the Ubiquitin-protein Ligase Nedd4 During Apoptosis. J. Biol. Chem. 273 13524-13530.

Waterhouse, N., Finucane, D., Green, D.R., Elce, J., Alnemri, E., Litwack, G., Khanna, K.K., Lavin, M.F. and Watters D. (1998) Calpain activation is upstream of Caspases in radiation-induced apoptosis. Cell Death and Differentiation.5, 1051-1061.

Masci PP, Whitaker AN, Sparrow LG, de Jersey J, Watters DJ, McCarthy M, Lavin MF and Gaffney PJ. (2000) Textilinins from Pseudonaja textilis textilis: Characterisation of two novel plasmin inhibitors, which inhibit bleeding in an animal model. Blood Coagulation and Fibrinolysis. 11, 1-9.

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