Membrane transport is essential for the growth, homeostasis and defence of cells. No better evidence of this fact is the considerable proportion of the genome devoted to membrane bound proteins. However, disruption of membrane transport often contributes to development, or progression, of many disease states. In addition, perturbations in membrane transport processes frequently contribute to the failure of many therapeutic strategies. Our research interests focus on understanding the contributions of membrane transport processes to disease and overcoming their impact in treating disease. The expertise of our research team is in the biochemical pharmacology of membrane transporters and generating structural information on these proteins. As shown by the diagram opposite, our strategy utilises the triad of structural, functional and pharmacological endeavours. The laboratory has assembled the infrastructure and considerable expertise in enabling us to work within this triad. We have four main streams of research, so click on the appropriate one and see more details on each of the major projects that we deal with:
- Contributions of ABC transporters (P-glycoprotein and ABCG2) to chemotherapy resistance in cancer.
- Does faulty retinoid transport (by ABCA4) underpin several visual disorders?
- Malarial resistance to chemotherapy and drug translocation.
- Adaptive changes to bioenergetic metabolism and nutrient utilisation in solid tumours.
Open to students
Do multidrug transporters play a role in Alzheimer’s Disease? (Undergraduate, Honours, Graduate, Higher degree by research)
Lipid flipping in vision: seeing is believing! (Honours, Graduate, Higher degree by research)
Starving tumours (Honours, Graduate, Higher degree by research)
Why does cancer chemotherapy fail? (Honours, Higher degree by research)
Selected research articles (related to research themes)
- Mellor H.R., and Callaghan R (2011) Accumulation and distribution of doxorubicin in tumour spheroids: the influence of acidity and expression of P-glycoprotein. Cancer Chemotherapy & Pharmacology 68, 1179-1190
- Crowley, E., O'Mara, M. L., Kerr, I. D., and Callaghan, R. (2010) Trans-membrane helix 12 plays a pivotal role in coupling energy provision and drug binding in ABCB1. FEBS Journal. 277(19):3974-85
- Crowley E, O'Mara ML, Reynolds C, Tieleman DP, Storm J, Kerr ID & Callaghan R (2009)Transmembrane helix 12 modulates progression of the ATP catalytic cycle in ABCB1.Biochemistry 48, 6249-6258
- McDevitt, C., Collins, R. F., Conway, M., Storm, J., Kerr, I. D., Ford, R. C., and Callaghan, R. (2006). Purification and 3-D structural analysis of oligomeric human multidrug transporter ABCG2.Structure 14, 1623-1632
- Clark, R., Kerr, I. D., and Callaghan, R. (2006). Multiple drug binding sites on the ABCG2 transporter. British Journal of Pharmacology 149, 506-515
- Mellor, H. R., Davies, L. A., Caspar, H., Pringle, C. R., Hyde, S. C., Gill, D. R., and Callaghan, R. (2006). Optimising non-viral gene delivery in a tumour spheroid model. J Gene Medicine 8, 1160-1170.
Selected review articles
- Pollock N.L., and Callaghan R. (2011) The Lipid Translocase, ABCA4: seeing is believing. FEBS Journal 278, 3204-3214
- Crowley, E., and Callaghan, R. (2010) Multidrug efflux pumps: drug binding - gates or cavity? FEBS Journal 277, 530-539
- Callaghan R, Crowley E, Potter S, and Kerr ID (2008) P-glycoprotein: So Many Ways to Turn It On.J Clinical Pharmacology 48:365-378
- McDevitt C and Callaghan R. (2007). How can we best use structural information on P-glycoprotein to design inhibitors? Pharmacology & Therapeutics. 113, 429-441.