1. The early-Australian Years
I conducted my undergraduate studies in Science at the University of Melbourne and obtained a BSc (Hons) with a combined major in Biochemistry and Pharmacology in 1986. The following year I began my PhD studies at the Clinical Pharmacology Unit at St Vincent’s Hospital, also a part of the University of Melbourne. My project focussed on the resistance of conjugative drug metabolising systems to acute and chronic liver injury. I obtained my PhD from the University in 1990.
2. The Canadian Adventure
In 1990 I spent a year in the Lipid Biophysics Laboratory at McMaster University in the cold expanses of Hamilton Ontario in Canada. The project focussed on the complex interaction between the multidrug transporter P-glycoprotein and its lipid environment. In 1991 I joined the Cell Biology Laboratory at the University of Toronto. During this period I focussed on the ABC family of transporters. In particular, I explored the pharmacology of P-glycoprotein and the potential for protein therapy with CFTR to restore chloride flux in lung epithelial cells.
3. The English Way
In 1993 I left sunny Canada for England and the dreaming spires of Oxford. I joined the ICRF Laboratories at the Institute of Molecular Medicine at the University of Oxford. My research focus was on the biochemical pharmacology and structure of the drug transporter P-glycoprotein. In 1997 I graduated from post-doctoral work to head my own research group in the Department of Clinical Laboratory Sciences at the University of Oxford. I was also made a Fellow of Merton College Oxford where I taught Medical Biochemistry and Structural Biochemistry. The primary research focus of my group was the contribution of drug transport process to human diseases.
4. Back to Australia
In February 2012 I returned to Australia to take up a post as Associate Professor at ANU. I hold a cross appointment between the Research School of Biology and the Medical School. My research interests will build on those founded in Oxford; namely understanding transport processes related to human disease. I will teach biochemistry to medical students and run the medical school research project component.
Selected research articles (last 10 years only)
1 Skrzypek, R. & Callaghan, R. The "pushmi-pullyu" of resistance to chloroquine in malaria. Essays Biochem 61, 167-175 (2017).
2 Mittra, R. et al. Location of contact residues in pharmacologically distinct drug binding sites on P-glycoprotein. Biochem Pharmacol 123, 19-28 (2017).
3 Board, M. et al. Acetoacetate is a more efficient energy-yielding substrate for human mesenchymal stem cells than glucose and generates fewer reactive oxygen species. Int J Biochem Cell Biol 88, 75-83, (2017).
4 Smith, H. et al. The Effects of Severe Hypoxia on Glycolytic Flux and Enzyme Activity in a Model of Solid Tumors. J Cell Biochem 117, 1890-1901, (2016).
5 Mittra, R., Coyle, E. & Callaghan, R. in ABC Transporters - 40 Years on (ed Anthony M. George) Ch. 8, 153-194 (Springer International Publishing, 2016).
6 Darby, R. A., Unsworth, A., Knapp, S., Kerr, I. D. & Callaghan, R. Overcoming ABCG2-mediated drug resistance with imidazo-[1,2-b]-pyridazine-based Pim1 kinase inhibitors. Cancer Chemother Pharmacol 76, 853-864, (2015).
7 Callaghan, R. Providing a molecular mechanism for P-glycoprotein; why would I bother? Biochem Soc Trans 43, 995-1002, (2015).
8 van Wonderen, J. H. et al. The central cavity of ABCB1 undergoes alternating access during ATP hydrolysis. FEBS J 281, 2190-2201,(2014).
9 Pollock, N. L. et al. Improving the stability and function of purified ABCB1 and ABCA4: The influence of membrane lipids. Biochim Biophys Acta 1838, 134-147, (2014).
10 Debono, A. J. et al. The synthesis and biological evaluation of multifunctionalised derivatives of noscapine as cytotoxic agents. ChemMedChem 9, 399-410, (2014).
11 Callaghan, R., Luk, F. & Bebawy, M. Inhibition of the multidrug resistance P-glycoprotein: time for a change of strategy? Drug Metab Dispos 42, 623-631, (2014).
12 Bloch, K. et al. Metabolic alterations during the growth of tumour spheroids. Cell Biochem Biophys 68, 615-628, (2014).
13 Pluchino, K. M., Hall, M. D., Goldsborough, A. S., Callaghan, R. & Gottesman, M. M. Collateral sensitivity as a strategy against cancer multidrug resistance. Drug Resist Updat 15, 98-105, (2012).
14 Espinosa, M. et al. Survivin isoform Delta Ex3 regulates tumor spheroid formation. Cancer Lett 318, 61-67, (2012).
15 Callaghan, R., George, A. M. & Kerr, I. D. in Comprehensive Biophysics (ed H. Egelman Editor-in-Chief: Edward) 145-173 (Elsevier, 2012).
16 Pollock, N. L., Niesten, P. & Callaghan, R. in Membrane Asymmetry & Transmembrane Motion of Lipids (eds A. Herrman & P. F. Devaux) Ch. 11, 225-249 (John Wiley & Sons, 2011).
17 Pollock, N. L. & Callaghan, R. The lipid translocase, ABCA4: seeing is believing. FEBS J 278, 3204-3214, (2011).
18 Mellor, H. R. & Callaghan, R. Accumulation and distribution of doxorubicin in tumour spheroids: the influence of acidity and expression of P-glycoprotein. Cancer Chemother Pharmacol 68, 1179-1190 (2011).
19 Darby, R. A. J., Callaghan, R. & McMahon, R. M. P-glycoprotein Inhibition: The Past, the Present and the Future. Current Drug Metabolism 12, 722-731 (2011).
20 Jeyabalan, J. et al. SEDLIN forms homodimers: characterisation of SEDLIN mutations and their interactions with transcription factors MBP1, PITX1 and SF1. PLoS One 5, e10646, doi:10.1371/journal.pone.0010646 (2010).
21 Crowley, E., O'Mara, M. L., Kerr, I. D. & Callaghan, R. Transmembrane helix 12 plays a pivotal role in coupling energy provision and drug binding in ABCB1. FEBS J 277, 3974-3985, (2010).
22 Crowley, E., McDevitt, C. A. & Callaghan, R. Generating inhibitors of P-glycoprotein: where to, now? Methods Mol Biol 596, 405-432, (2010).
23 Crowley, E. & Callaghan, R. Multidrug efflux pumps: drug binding - gates or cavity? FEBS Journal 277, 530-539, (2010).
24 Callaghan, R. Multidrug efflux pumps: the big issues. FEBS J 277, 529, (2010).
25 McDevitt, C. A., Collins, R., Kerr, I. D. & Callaghan, R. Purification and structural analyses of ABCG2. Adv Drug Deliv Rev 61, 57-65, (2009).
26 Heikal, A. et al. The stabilisation of purified, reconstituted P-glycoprotein by freeze drying with disaccharides. Cryobiology 58, 37-44, (2009).
27 Ford, R. C., Kamis, A. B., Kerr, I. D. & Callaghan, R. in Transporters as drug carriers (eds G.F. Ecker & P. Chiba) (Wiley-VCH, 2009).
28 Crowley, E. et al. Transmembrane helix 12 modulates progression of the ATP catalytic cycle in ABCB1. Biochemistry 48, 6249-6258, (2009).
29 Storm, J. et al. Cytosolic region of TM6 in P-glycoprotein: topographical analysis and functional perturbation by site directed labeling. Biochemistry 47, 3615-3624, (2008).
30 Rivers, F., O'Brien, T. J. & Callaghan, R. Exploring the possible interaction between anti-epilepsy drugs and multidrug efflux pumps; in vitro observations. Eur J Pharmacol 598, 1-8, (2008).
31 Mellor, H. R. & Callaghan, R. Resistance to chemotherapy in cancer: a complex and integrated cellular response. Pharmacology 81, 275-300, (2008).
32 McHugh, K. & Callaghan, R. in Multidrug Resistance: Biological and Pharmaceutical Advances in Antitumour Treatment (ed N.A. Colabufo) Ch. 7, 321-353 (Research Signpost, 2008).
33 McDevitt, C. A. et al. Structural insights into P-glycoprotein (ABCB1) by small angle X-ray scattering and electron crystallography. FEBS Lett 582, 2950-2956, (2008).
34 McDevitt, C. A. et al. Is ATP binding responsible for initiating drug translocation by the multidrug transporter ABCG2? FEBS J 275, 4354-4362, (2008).
35 Carrier, D. J. et al. The binding of auxin to the Arabidopsis auxin influx transporter AUX1. Plant Physiol 148, 529-535, (2008).
36 Callaghan, R., Crowley, E., Potter, S. & Kerr, I. D. P-glycloprotein: So many ways to turn it on. Journal of Clinical Pharmacology 48, 365-378, (2008).
37 Callaghan, R. & Crowley, E. in Horizons in Medicine Vol. 20 (ed P. Mathieson) 197-207 (Royal College of Physicians, 2008).
38 Storm, J. et al. Residue G346 in transmembrane segment six is involved in inter-domain communication in P-glycoprotein. Biochemistry 46, 9899-9910, (2007).
39 Modok, S. et al. Transport kinetics of four- and six-coordinate platinum compounds in the multicell layer tumour model. Br J Cancer 97, 194-200, (2007).
40 McDevitt, C. A. & Callaghan, R. How can we best use structural information on P-glycoprotein to design inhibitors? Pharmacol Ther 113, 429-441, (2007).
41 Hall, M. D., Mellor, H. R., Callaghan, R. & Hambley, T. W. Basis for design and development of platinum(IV) anticancer complexes. J Med Chem 50, 3403-3411, (2007).
42 Alderden, R. A. et al. Elemental tomography of cancer-cell spheroids reveals incomplete uptake of both platinum(II) and platinum(IV) complexes. J Am Chem Soc 129, 13400-13401, (2007).
- Lecturer & Discipline Leader in Medical Biochemistry to Year 1 MChD students
- Chair of the MChD Research Projects Committee
- Lecturer in BIOL2171 - energy metabolism and biomembranes
- Lecturer in BIOL2174 - active transport mechanisms
- Lecturer in BIOL3108 - cancer chemotherapy and resistance