Research Interests

My current research is into the molecular biology of drug and radiation resistance in the treatment of cancer specifically, biochemistry of resistance, induction of resistance and the mechanism of action of radiation and drugs used in the treatment of cancer.

This background has provided the basis for expanding my research to drug resistance in parasites and more specifically, nematodes.

Projects

Validation of thiol metabolism as a drug target  in Haemonchus contortus

The project will characterise glutamylcysteine synthetase (GCase), the rate-limiting step in glutathione synthesis, and thioredoxin reductase, which maintains the reduced cellular thioredoxin in Haemonchus contortus.  The main aim of these studies is to provide “proof of concept” that these enzymes are potential drug-targets for the control of H. contortus in sheep.  This will be achieved by the following:

i. Determine the substrate specificity of the enzymes and the effect of inhibitors of activity.

ii. Testing, in vitro, the ability of selected inhibitory compounds alone, and in combination, to inhibit viability/motility of H.contortus and other strongylids.

iii. Molecular cloning of these enzymes from H. contortus, necessary for the development of a high-throughput screening assay to identify new inhibitors of enzyme activity.

Drug resistance in cancer cells

Drug resistance is problem in the treatment of cancer and other diseases.  Multidrug resistance is associated with the increased expression of one or several different molecules resulting in a decreased level of drug reaching its cellular target.  The goal of this research is to understanding the cellular changes associated with the development of resistance to drugs to identify alternate drug targets and to prevent, or circumvent, the development of resistance. 

Selected Publications

1. Henness S, Davey MW, Harvie RM, Banyer J, Wasinger V, Corthals G, Davey RA (2004) Changes in gene expression associated with stable drug and radiation resistance in small cell lung cancer cells are similar to those caused by a single X-ray dose.  Radiation Research 161, 495-503.

2. Davey RA, Locke VL, Henness S, Harvie RM, Davey MW (2004) Cellular models of drug and radiation resistant small cell lung cancer cells. Anticancer Research, 24, 465-472.

3. Locke VL, Davey RA, Davey MW (2003) Modulation of drug and radiation resistance in small cell lung cancer cells by paclitaxel. Anti-Cancer Drugs, 14, 523-531.

4. Henness S, Davey MW, Harvie RM, Davey RA (2002) Fractionated irradiation of H69 small cell lung cancer cells causes stable radiation and drug resistance with increased MRP1, MRP2 and topoisomerase IIa Expression.  International Journal of Radiation Oncology, Biology and Physics 54, 898-905.

5. Cullen KV, Davey RA, Davey MW (2001) Verapamil-stimulated glutathione transport by the multidrug resistance-associated protein (MRP1) in leukaemia cells. Biochemical Pharmacology 62, 417-424.

Research Team

Assoc. Prof. Mary Davey  (Chief investigator, IBID)
Prof. John Ellis (Chief investigator, Medical and Molecular Biosciences, UTS)
Amanda Hudson (PhD student)
Irene Sotirchos (PhD student)
Catherine James (PhD student)