Associate Professor Richard Callaghan

BSc(Hons), PhD
Associate Professor in Biochemistry
Chair Medical School Research Project Committee
  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 build on those founded in Oxford; namely understanding transport processes related to human disease. I teach biochemistry to medical students and run the medical school research project component.

Specialisation

  • Biochemistry
  • Cell Biology
  • Microbiology
  • Pharmacology

Research interests

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 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:

  1. Contributions of ABC transporters (P-glycoprotein and ABCG2) to chemotherapy resistance in cancer.
  2. Does faulty retinoid transport (by ABCA4) underpin several visual disorders?
  3. Malarial resistance to chemotherapy and drug translocation.
  4. Adaptive changes to bioenergetic metabolism and nutrient utilisation in solid tumours
  • Chai, A, Leung, G, Callaghan, R et al 2020, 'P-glycoprotein: a role in the export of amyloid-beta in Alzheimer's disease?', The FEBS Journal, vol. 287, no. 4, pp. 612-625.
  • Muthiah, D, Henshaw, G, DeBono, A et al 2019, 'Overcoming P-Glycoprotein-Mediated Drug Resistance with Noscapine Derivatives', Drug Metabolism and Disposition, vol. 47, no. 2, pp. 164-172.
  • Yuan, Y, Cai, T, Callaghan, R et al 2019, 'Psoralen-loaded lipid-polymer hybrid nanoparticles enhance doxorubicin efficacy in multidrug-resistant HepG2 cells', International journal of nanomedicine, vol. 14, no. -, pp. 2207-2218.
  • Skrzypek, R, Iqbal, S & Callaghan, R 2018, 'Methods of reconstitution to investigate membrane protein function', Methods, vol. 147, pp. 126-141pp.
  • Devine, S, Yong, C, Amenuvegbe, D et al 2018, 'Synthesis and Pharmacological Evaluation of Noscapine-Inspired 5-Substituted Tetrahydroisoquinolines as Cytotoxic Agents', Journal of Medicinal Chemistry, vol. 61, no. 18, pp. 8444-8456pp.
  • Yuan, Y, Chiba, P, Cai, T et al 2018, 'Fabrication of psoralen-loaded lipid-polymer hybrid nanoparticles and their reversal effect on drug resistance of cancer cells', Oncology Reports, vol. 40, no. 2, pp. 1055-1063pp.
  • Board, M, Lopez, C, van den Bos, C et al 2017, 'Acetoacetate is a more efficient energy-yielding substrate for human mesenchymal stem cells than glucose and generates fewer reactive oxygen species', The International Journal of Biochemistry and Cell Biology, vol. 88, pp. 75-83.
  • Muthiah, D & Callaghan, R 2017, 'Dual effects of the PI3K inhibitor ZSTK474 on multidrug efflux pumps in resistant cancer cells', European Journal of Pharmacology, vol. 815, pp. 127-137.
  • Skrzypek, R & Callaghan, R 2017, 'The "pushmi-pullyu" of resistance to chloroquine in malaria', Essays in Biochemistry, vol. 61, no. 1, pp. 167-175.
  • Mittra, R, Pavy, M, Subramanian, N et al 2017, 'Location of contact residues in pharmacologically distinct drug binding sites on P-glycoprotein', Biochemical Pharmacology, vol. 123, pp. 19-28.
  • Smith, H, Board, M, Pellagatti, A et al 2016, 'The Effects of Severe Hypoxia on Glycolytic Flux and Enzyme Activity in a Model of Solid Tumors', Journal of Celluar Biochemistry, vol. 117, no. 8, pp. 1890-1901.
  • Mittra, R, Coyle, E & Callaghan, R 2016, 'Just How and Where Does P-glycoprotein Bind All Those Drugs?', in Anthony M George (ed.), ABC Transporters - 40 Years on, Springer International Publishing, Australia, pp. 153-194pp.
  • Darby, R, Unsworth, A, Knapp, S et al 2015, 'Overcoming ABCG2-mediated drug resistance with imidazo-[1,2-b]-pyridazine-based Pim1 kinase inhibitors', Cancer Chemotherapy and Pharmacology, vol. 76, no. 4, pp. 853-864.
  • Callaghan, R 2015, 'Providing a molecular mechanism for P-glycoprotein; Why would i bother?', Biochemical Society Transactions, vol. 43, no. 5, pp. 995-1002.
  • van Wonderen, J, McMahon, R, O'Mara, M et al 2014, 'The central cavity of ABCB1 undergoes alternating access during ATP hydrolysis', The FEBS Journal, vol. 281, no. 9, pp. 2190-2201.
  • Pollock, N, McDevitt, C, Collins, R et al 2014, 'Improving the stability and function of purified ABCB1 and ABCA4: The influence of membrane lipids', Biochimica et Biophysica Acta: Biomembranes, vol. 1838, no. 1, pp. 134-147.
  • DeBono, A, Mistry, S, Xie, J et al 2014, 'The Synthesis and Biological Evaluation of Multifunctionalised Derivatives of Noscapine as Cytotoxic Agents', ChemMedChem, vol. 9, no. 2, pp. 399-410.
  • Callaghan, R, Bloch, K, Smith, H et al 2014, 'Metabolic Alterations During the Growth of Tumour Spheroids', Cell Biochemistry and Biophysics, vol. 68, no. 3, pp. 615-628.
  • Callaghan, R, Luk, F & Bebawy, M 2014, 'Inhibition of the multidrug resistance P-glycoprotein: time for a change of strategy?', Drug Metabolism and Disposition, vol. 42, no. 4, pp. 623-631.
  • van Wonderen, J, McMahon, R, O'Mara, ML et al 2014, 'The central cavity of ABCB1 undergoes alternating access during ATP hydrolysis', The FEBS Journal, vol. 281, no. 9, pp. 2190-2201
  • Callaghan, R, Pluchino, K, Hall, M et al 2012, 'Collateral sensitivity as a strategy against cancer multidrug resistance', Drug Resistance Updates, vol. 15, no. 1-2, pp. 98-105.
  • Callaghan, R, George, A & Kerr, I 2012, 'Molecular Aspects of the Translocation Process by ABC Proteins', in Edward H. Egelman (ed.), Comprehensive Biophysics, Vol 8, Bioenergetics, Academic Press, Oxford, pp. 145-173.
  • Espinosa, M, Ceballos-Cancino, G, Callaghan, R et al 2012, 'Survivin isoform Delta Ex3 regulates tumor spheroid formation', Cancer Letters, vol. 318, no. 1, pp. 61-67.
  • Pollock, N & Callaghan, R 2011, 'The lipid translocase, ABCA4: seeing is believings', The FEBS Journal, vol. 278, no. 18, pp. 3204-3214.
  • Mellor, H & Callaghan, R 2011, 'Accumulation and distribution of doxorubicin in tumour spheroids: the influence of acidity and expression of P-glycoprotein', Cancer Chemotherapy and Pharmacology, vol. 68, no. 5, pp. 1179-1190.
  • Darby, R, Callaghan, R & McMahon, R 2011, 'P-glycoprotein Inhibition: The Past, the Present and the Future', Current Drug Metabolism, vol. 12, no. 8, pp. 722-731.
  • Pollock, N, Niesten, P & Callaghan, R 2011, 'The flippase delusion', in Philippe F. Devaux & Andreas Herrmann (ed.), Transmembrane Dynamics of Lipids, John Wiley & Sons Inc, Hoboken, New Jersey, USA, pp. 225-249.
  • Callaghan, R 2010, 'Multidrug efflux pumps: the big issues', The FEBS Journal, vol. 277, no. 3, p. 529.
  • Crowley, E & Callaghan, R 2010, 'Multidrug efflux pumps: drug binding - gates or cavity?', The FEBS Journal, vol. 277, no. 3, pp. 530-539.
  • Crowley, E, McDevitt, C & Callaghan, R 2010, 'Generating Inhibitors of P-Glycoprotein: Where to, Now?', Methods in Molecular Biology, vol. 596, pp. 405-432.
  • Jeyabalan, J, Mesbit, M, Galvanovskis, J et al 2010, 'SEDLIN forms homodimers: Characterisation of SEDLIN mutations and their interactions with transcription factors MBP1, PITX1 and SF1', PLOS ONE (Public Library of Science), vol. 5, no. 5.
  • Crowley, E, O'Mara, M, Kerr, I et al 2010, 'Transmembrane helix 12 plays a pivotal role in coupling energy provision and drug binding in ABCB1', The FEBS Journal, vol. 277, no. 19, pp. 3974-3985.
  • McDevitt, C, Collins, R, Kerr, I et al 2009, 'Purification and structural analyses of ABCG2', Advanced Drug Delivery Reviews, vol. 61, no. 1, pp. 57-65.
  • Heikal, A, Box, K, Rothnie, A et al 2009, 'The stabilisation of purified, reconstituted P-glycoprotein by freeze drying with disaccharides', Cryobiology, vol. 58, no. 1, pp. 37-44.
  • Ford, R, Kamis, A, Kerr, I et al 2009, 'The ABC Transporters: Structural Insights into Drug Transport', in Gerhard Ecker & Peter Chiba (ed.), Transporters as Drug Carriers: Structure, Function, Substrates., Wiley-VCH Verlag GmbH & Co. KGaA., United States, pp. 1-48.
  • Crowley, E, O'Mara, ML, Reynolds, C et al 2009, 'Transmembrane helix 12 modulates progression of the ATP catalytic cycle in ABCB1', Biochemistry, vol. 48, no. 26, pp. 6249-6258.
  • Callaghan, R, Crowley, E, Potter, S et al 2008, 'P-glycoprotein: So many ways to turn it on', Journal of Clinical Pharmacology, vol. 48, no. 3, pp. 365-378.
  • Rivers, F, O'Brien, T & Callaghan, R 2008, 'Exploring the possible interaction between anti-epilepsy drugs and multidrug efflux pumps; in vitro observations', European Journal of Pharmacology, vol. 598, no. 1-3, pp. 1-8.
  • Carrier, D, Bakar, N, Napier, R et al 2008, 'The binding of auxin to the arabidopsis auxin influx transporter AUX1', Plant Physiology, vol. 148, no. 1, pp. 529-535.
  • Mellor, H & Callaghan, R 2008, 'Resistance to chemotherapy in cancer: A complex and integrated cellular response', Pharmacology, vol. 81, no. 4, pp. 275-300.
  • Callaghan, R & Crowley, E 2008, 'Chemoresistance in cancer', Horizons in Medicine, vol. 20, pp. 197-207.
  • McDevitt, C, Crowley, E, Hobbs, G et al 2008, 'Is ATP binding responsible for initiating drug translocation by the multidrug transporter ABCG2?', The FEBS Journal, vol. 275, no. 17, pp. 4354-4362.
  • Storm, J, Modok, S, O'Mara, M et al 2008, 'Cytosolic region of TM6 in P-glycoprotein: Topographical analysis and functional perturbation by site directed labeling', Biochemistry, vol. 47, no. 12, pp. 3615-3624.
  • McDevitt, C, Shintre, C, Grossmann, J et al 2008, 'Structural insights into P-glycoprotein (ABCB1) by small angle X-ray scattering and electron crystallography', FEBS Letters, vol. 582, no. 19, pp. 2950-2956.
  • Modok, S, Scott, R, Alderden, R et al 2007, 'Transport kinetics of four- and six-coordinate platinum compounds in the multicell layer tumour model', British Journal of Cancer, vol. 97, no. 2, pp. 194-200.
  • Storm, J, O'Mara, ML, Crowley, E et al 2007, 'Residue G346 in Transmembrane Segment Six is Involved in Inter-Domain Communication in P-Glycoprotein', Biochemistry, vol. 46, no. 35, pp. 9899-9910.
  • Callaghan, R, Ford, R & Kerr, I 2006, 'The translocation mechanism of P-glycoprotein', FEBS Letters, vol. 580, no. 4, pp. 1056-1063.
  • Rosenberg, M, Callaghan, R, Modok, S et al 2005, 'Three-dimensional structure of P-glycoprotein: The transmembrane regions adopt an asymmetric configuration in the nucleotide-bound state', Journal of Biological Chemistry, vol. 280, no. 4, pp. 2857-2862.
  • MEDI8011 Lecturer & Discipline Leader in Medical Biochemistry
  • MEDI8013 Chair of the MChD Research Projects Committee
  • BIOL2171 - Biochemistry & nutrition
  • BIOL2174 - Cell physiology in health & disease
  • BIOL3108 - Hallmarks of cancer