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 five 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 drug efflux pumps to chemotherapy resistance in cancer.
- Do faulty retinal transport processes underpin visual disorders?
- Molecular mechanisms of transporters conferring resistance to chemotherapy of malaria
- Adaptive changes to bioenergetic metabolism and nutrient utilisation in solid tumours.
- The contributions of ABC transporters to amyloid protein clearance from the CNS.
Selected research articles (related to research themes)
- Mittra, R., Pavy, M., Subramanian, N., George, A.M., O'Mara, M.L., Kerr, I.D., Callaghan, R., 2017. Location of contact residues in pharmacologically distinct drug binding sites on P-glycoprotein. Biochem Pharmacol 123, 19-28.
- Smith, H., Board, M., Pellagatti, A., Turley, H., Boultwood, J., Callaghan, R., 2016. The Effects of Severe Hypoxia on Glycolytic Flux and Enzyme Activity in a Model of Solid Tumors. J Cell Biochem 117, 1890-1901.
- Darby, R.A., Unsworth, A., Knapp, S., Kerr, I.D., Callaghan, R., 2015. Overcoming ABCG2-mediated drug resistance with imidazo-[1,2-b]-pyridazine-based Pim1 kinase inhibitors. Cancer Chemother Pharmacol 76, 853-864.
- Pollock, N.L., McDevitt, C.A., Collins, R., Niesten, P.H., Prince, S., Kerr, I.D., Ford, R.C., Callaghan, R., 2014. Improving the stability and function of purified ABCB1 and ABCA4: The influence of membrane lipids. Biochim Biophys Acta 1838, 134-147.
- Bloch, K., Smith, H., van Hamel Parsons, V., Gavaghan, D., Kelly, C., Fletcher, A., Maini, P., Callaghan, R., 2014. Metabolic alterations during the growth of tumour spheroids. Cell Biochem Biophys 68, 615-628.
- Debono, A.J., Mistry, S.J., Xie, J., Muthiah, D., Phillips, J., Ventura, S., Callaghan, R., Pouton, C.W., Capuano, B., Scammells, P.J., 2014. The synthesis and biological evaluation of multifunctionalised derivatives of noscapine as cytotoxic agents. ChemMedChem 9, 399-410.
- Crowley, E., O'Mara, M.L., Kerr, I.D., Callaghan, R., 2010. Transmembrane helix 12 plays a pivotal role in coupling energy provision and drug binding in ABCB1. FEBS J 277, 3974-3985.
Selected review articles
- Skrzypek, R., Callaghan, R., 2017. The "pushmi-pullyu" of resistance to chloroquine in malaria. Essays Biochem 61, 167-175.
- Callaghan, R., 2015. Providing a molecular mechanism for P-glycoprotein; why would I bother? Biochem Soc Trans 43, 995-1002.
- Callaghan, R., Luk, F., Bebawy, M., 2014. Inhibition of the multidrug resistance P-glycoprotein: time for a change of strategy? Drug Metab Dispos 42, 623-631.
- Pluchino, K.M., Hall, M.D., Goldsborough, A.S., Callaghan, R., Gottesman, M.M., 2012. Collateral sensitivity as a strategy against cancer multidrug resistance. Drug Resist Updat 15, 98-105.
- Pollock, N.L., Callaghan, R., 2011. The lipid translocase, ABCA4: seeing is believing. FEBS J 278, 3204-3214.
- Darby, R.A.J., Callaghan, R., McMahon, R.M., 2011. P-glycoprotein Inhibition: The Past, the Present and the Future. Current Drug Metabolism 12, 722-731.