Callaghan, Richard - The Australian National University

个人简介

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.

研究领域

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

近期论文

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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.