Professor Basil Roufogalis
MPharm PhD DSc
University of Sydney
Phone: +61 2 9351 3391
Fax: +61 2 9351 4391
Pharmacy Building A15
The University of Sydney
NSW 2006 Australia
- Calcium translocating ATPase pumps and inhibitors
- Multi drug resistance in cancer
- Calcium regulation of cellular signalling by GTP-binding proteins
- Mechanisms of herbal medicines
- New therapeutic agents from medicinal herbs in pain, diabetes, hyperlipidemia and cancer
- Herb-drug interactions
- The role of small G-proteins in cellular function. Our laboratory was the first to report the Ca2+/calmodulin sensitivity of a small G-protein, subsequently identified as Ral-A. The role of Ral-A in cellular function, particularly as a part of the exocyst complex involved in exo/endocytosis in neuronal cells has been reported for the first time and its physiological function has been investigated. Recent studies identified an additional binding partner, the redox sensitive protein Erp57, and extensive mutation studies on both Ral-A and the Erp57 are being used to identify the physiological significance of this interaction in neuronal cell function (joint project with the Children’s Medical Research Institute)
- Overcoming multidrug resistance in cancer. The problem of multidrug resistance in cancer is responsible for failure of cancer chemotherapy. Projects have been undertaken to identify strategies for the reversal of this resistance, through detailed studies on the potential use of naturally occurring flavonoids to inhibit transport of drugs by P-glycoprotein, a protein pump overexpressed in resistant cells, including leukaemia cells. A new flavonoid has been identified as a potential new lead drug for reversing multidrug resistance, and is the subject of a PCT patent application. A second approach has been to investigate the mechanisms of traffic of P-glycoprotein in cells, using living cell fluorescence microscopy, with the aim of finding agents that can prevent the translocation of P-glycoprotein to the plasma membrane, where it pumps out the anticancer drugs. The interaction of P-glycoprotein with its transcription factors is also being investigated.
- Development of new analgesic/antiinflammatory agents based on their interaction with the capsaicin (TRPV-1) receptor (with Dr Colin Duke). An industry/university funded ARC SPIRT (now Linkage) grant allowed the investigation of the interaction of certain derivatives of gingerols, the pungent principles found in ginger, with the TRPV-1 receptor from primary rat dorsal root ganglia and in in vitro cyclooxygenase 1 and –2 assays. A synthetic chimeric hybrid gingerol/capsaicin molecule was obtained as a lead compound for further development as a drug candidate. An extract of ginger enriched in a gingerol active metabolite has been developed as a potential commercial extract with the partner company. The pure compounds and extracts were found to have significant anti-pain activity in animal models, in both acute and chronic pain models. The new molecules and their novel activities were granted international PCT patents in the US and Australia. The mechanism of interaction of antinociceptive agents with TRPV1 and related thermoreceptors, and the mechanism of regulation of these receptors by inflammatory activators and cell signalling pathways are under investigation.
- Development of cholesterol lowering agents. Research is being undertaken on a saponin fraction from the Chinese medicine Gynostemma pentaphyllum for development as an alternative medicine for the treatment of hypertriglyceridemia, high cholesterol and atherosclerosis, with minimum side effects. Chemical studies have identified new molecules with novel activities described for the first time against PPAR-alpha receptors in the liver and heart (with Dr Colin Duke). The consequences of PPAR-alpha mediated gene transcription on downstream pathways (eg tissue factor and metalloproteinases) is being investigated. Development of antidiabetic agents from Ayurvedic, Chinese and Western medicinal plants. A series of more than 12 recent publications in high impact journalshas elucidated the mechanisms behind the traditional use of plants, including Punica granatum, Salacia oblonga, Panax notoginsengand a berry shoot extract in lowering glucose and improving glucose tolerance in various type-2 diabetes models. Furthermore, the ability of these extracts, and in some cases their isolated active constituents, has been investigated on preventing the complications of diabetes, including cardiac fibrosis and liver steatosis, using gene transcription and translation techniques together with functional studies. Important mechanisms elucidated include interaction with PPAR-gamma receptors, modulation of iNOS, NFκB and FATP genes and their protein products, and the alpha-glucosidase enzyme responsible for postprandial hyperglycemia (with Dr Yuhao Li and Dr George Li).
- Immune-stimualation to enhance the outcome of cancer chemotherapy. Recent introduction of the cancer immunology group of Dr Daniel Sze into my laboratory has led to various collaborative projects aimed at screening Chinese and other medicines for positive immune stimulating and cancer cell cytotoxic activity in multiple myeloma. Techniques of phytochemistry and cell based assays are being developed to progress these cancer cell biology studies.
- Prevention of diabetic retinopathy is being studies in a retinal epithelial cell line. Taurine, a major component of Goji berry, has been found to activate PPAR-gamma and to alter apoptosis and junctional permeabilty in these retinal cells
- Non-alcoholic fatty liver disease (NAFLD) is difficult to treat by western medicine. A cell model of steatosis and steatohepatitis in NAFLD has been established to screen for lipid droplet formation in liver cells. A variety of ginsenosides and metabolites (especially compound K) were examined for prevention of NAFLD and found to affect PPAR-alpha and its downstream targets.
Professional Employment Record
- 1968 - 1969 Postdoctoral Fellow, Department of Chemistry, Division of Biochemistry, University of Ottawa.
- 1969 - 1975 Assistant Professor and Medical Research Council of Canada Scholar, University of British Columbia, Vancouver, Canada.
- 1980 - 1989 Associate Professor and Professor, University of British Columbia, Vancouver.
- 1986 - 1989 NH&MRC Senior Research Fellow, University of Sydney.
- 1989 - present Professor of Pharmaceutical Chemistry, University of Sydney.
- 2003-2005 Head of Department of Pharmacy, University of Sydney.
- 1997 - 2011 Executive Director, Herbal Medicines Research and Education Centre, University of Sydney
- 2000 - 2008 Pro Dean, Faculty of Pharmacy, University of Sydney
- 1990 - 1997 Organiser and Chair, Sydney Signal Transduction Group
- 1990 - 1997 NHMRC Major Equipment Committee
- 1991, 1999 DSc Assessment Committees (ad hoc)
- 1992, 1995 Department of Pharmacology and Bill Walsh Cancer Research Laboratories Review Committees
- 1992 - 1995 Sydney University Macromolecualr Analysis Facility Committee (SUMAC, SUPAMAC)
- 1990 - 1993 Faculty of Science Research Committee
- 1995 - 1997 University Research Grants (URG) Committee
- 1992 - 1995 Faculty of Science Associate Professor Promotions Committee
- 1993 - 2004 Member, Pharmacy Research Trust Grants Committee
- 1995, 1997 Faculty of Science Chair and Personal Chair Selection Committees
- 2000 Faculty of Science U2000 Fellowship Committee
- 1997 Faculty of Science First Year Coordinator Selection Committee
- 1999 Small ARC Grants Committee
- 2001 - 2004 Central University Level D Senior Appointments Committee
- 2001 Pharmaceutics Chair Selection Committee
- 2002 - 2004 AMA Complementary Medicines Policy Advisory Committee (adviser)
- 2005/6 AMA Therapeutics Committee (adviser)
- 2005 Government Advisory Committee on the regulation of complementary medicine practitioners
- 2004/05 Consultant (EqiTX Pty Ltd)
- 2004/6 Consultancy Reports to Herbal Medicines Companies (various)
- 2007 Interim Consultative Committee, National Institute of Complementary Medicine
- 2007/8 Chair, Scientific Committee, 3rd International Congress Complementary Medicines Research
- 2008 National Institute of Complementary Medicine (NICM) Scientific Advisory Board
- 2009 Member, Pharmaceutical Sciences Program Advisory Committee, School of Medical Sciences, RMIT
- 2010 China Studies Centre, Convenor of the Traditional Chinese Medicine Academic Group
- 2010 Member, China Studies Centre Executive Committee
- 2010 Elected Member, China Studies Centre Research Committee
- 2011 Deputy Chair, Scientific Committee, Integrative Medicine Forum and Exhibition, Sydney
- 2011 China Studies Centre Executive Committee, China Studies Centre Research Committee, China Studies centre TCM Academic Research Group Convenor (16 members)
- 2011 Successfully completed publication of a Special Issue of Current Pharmaceutical Biotechnology as Guest Editor (joint with Thomas Grewal). It included 10 invited papers from at least five different countries.
- 2012 Convenor, Mechanism-Based Natural Product Development Conference, Whistler Convention Center, B.C., Canada
- Song MK, Roufogalis, BD., Huang TH (2012). Reversal of the caspase-dependent apoptotic cytotoxicity pathway by taurine from Lycium barbarum (Goji Berry) in human retinal pigment epithelial cells: potential benefit in diabetic retinopathy. Evidence-Based Complementary and Alternative Medicine. (In Press).
- Roufogalis BD, Grewal T. (2012) New methodology and approaches to intracellular lipid transport in atherosclerosis and cardiovascular disease. Editorial. Curr Pharm Biotech. 13 276-277.
- Kim, M.S, Kung, S., Grewal, T. Roufogalis, BD*. (2012 Methodologies for investigating natural medicines for the treatment of nonalcoholic fatty liver disease (NAFLD). Curr Pharm Biotech. 13 278-291.
- Song, MK., Roufogalis, BD., Huang, TH-W. (2012) Modulation of Diabetic Retinopathy Pathophysiology by Natural Medicines through PPAR-γ-related Pharmacology. British Journal of Pharmacology. 165:1: 4-19.
- Roufogalis, BD., Kota, BP. (2012) Pharmacology of medicinal Plants and their active principles used in the treatment of gastrointestinal tract disorders. Gastroenterology, ISBN 979-953-307-495-4. Accepted for publication, November 7, 2011 (book chapter)
- Li, X.L., Roufogalis, BD., Nammi, S., Heather, A., McGrath, K. (2012) Attenuation of Liver Pro-Inflammatory Responses by Zingiber officinale via Inhibition of NF-kappa B Activation in High-Fat Diet-Fed Rats. Basic & Clinical Pharmacology & Toxicology. 110 (3) 238-244.
- Song, MK., Roufogalis, BD., Huang, THW. (2011) Modulation of RAGE and the Downstream Targets of RAGE Signaling Cascades by Taurine in Lycium Barbarum (Goji Berry): Protection of Human Retinal Pigment Epithelial Barrier Function and its Potential Benefit in Diabetic Retinopathy. Journal of Diabetes & Metabolism. 2 (9) 162.
- Mandadi, S. , Armati, PJ. and Roufogalis, BD. (2011) Real-Time Translocation and Function of PKCβII Isoform in Response to Nociceptive Signaling via the TRPV1 Pain Receptor. Pharmaceuticals 4(11) 1503-1517.
- Mo, SL., Li, J., Loh, Y., Brown, R., Smith, A., Chen, Y., Joshua, D., Roufogalis, BD., Li, G., Fan, K., Ng, M., and Sze, DM. (2011) "Factors Influencing the Abundance Of the Side Population In a Human Myeloma Cell Line," Bone Marrow Research. Volume 2011, Article ID 524845, doi:10.1155/2011/524845.
- Huang, TH-W, Roufogalis BD. (2011) Healing the Diabetic Heart: Modulation of Cardiometabolic Syndrome through PPAR. Current Molecular Pharmacology (Pubmed Indexed). Accepted for publication, June 28, 2011.
- Song, MK., Salam, NK., Roufogalis, BD., Huang, TH. (2011) Lycium barbarum (Goji Berry) extracts and its taurine component inhibit PPAR-γ-dependent gene transcription in human retinal pigment epithelial cells: Possible implications for diabetic retinopathy treatment, Biochemical Pharmacology, 82 (9)1209-1218.
- Kota, B.P., Allen, J.D., Roufogalis, B.D. (2011) The effect of vitamin D3 and ketoconazole combination on VDR mediated P-gp expression and function in human colon adenocarcinoma cells: implications in drug disposition and resistance. Basic and Clinical Pharmacology and Toxicology, 109 (2): 97-102.
- Kota BP, Abdul MI, Allen JD, Kalagara M, Roufogalis BD. (2011) Effect of vitamin D3 supplementation on the pharmacokinetics of digoxin - A pilot study. Fundamental and Clinical Pharmacology. Accepted for publication, February 8, 2011.
- Tran, V.H, Marks, D., Duke, R.K., Bebawy, M., Duke, C.C. Roufogalis, B.D., (2011) Modulation of P-glycoprotein-mediated anticancer drug accumulation, Cytotoxicity and ATPase activity by flavonoid interactions". Nutrition and Cancer, 63(3), 435–443.
- Mandadi, S., Armati, PJ. Roufogalis, B.D. (2011) Protein kinase C modulation of thermo-sensitive TRP channels: Implications for pain signaling. Journal of Natural Science, Biology and Medicine, 2(1), 12-24.
- Kota, B P, Tran, V H, Allen, J D, Bebawy, M, Roufogalis, B D 2010, Characterization of PXR mediated P-glycoprotein regulation in intestinal LS174T cells, Pharmacological Research, 62(5), 426-431
- Mohammed Abdul, M I, Jiang, X, Williams, K, Day, R, Roufogalis, B D, Liauw, W, Xu, H, Matthias, A, Lehmann, R, McLachlan, A J 2010, Pharmacokinetic and pharmacodynamic interactions of echinacea and policosanol with warfarin in healthy subjects, British Journal of Clinical Pharmacology, 69(5), 508-515
- Omar, E, Kam, A, Alqahtani, A, Li, K M, Naumovski, V, Nammi, S, Chan, K, Roufogalis, B D, Li, Q 2010, Herbal Medicines and Nutraceuticals for Diabetic Vascular Complications: Mechanisms of Action and Bioactive Phytochemicals, Current Pharmaceutical Design, 16(34), 3776-3807
- Nammi, S., Sreemantula, S., and Roufogalis, B., 2010, Protective Effects of Ethanolic Extract of Zingiber officinale Rhizome on the Development of Metabolic Syndrome in High-Fat Diet-Fed Rats, Basic & Clinical Pharmacology & Toxicology, 106 (5) 389 – 395
- Huang, H. T., Teoh, A. ., Lin, B., Lin, D. S., and Roufogalis, B., 2009, The role of herbal PPAR modulators in the treatment of cardiometabolic syndrome, Pharmacological Research, 60, 195-206
- Nammi, S., Kim, M. S., Gavande, N., Li, Q., and Roufogalis, B., 2009, Regulation of Low-Density Lipoprotein Receptor and 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Expression by Zingiber officinale in the Liver of High-Fat Diet-Fed Rats, Basic & Clinical Pharmacology & Toxicology, 104 (5) 366 – 373