Crowe, Andrew - Curtin University

研究领域

I have 4 current interests: Firstly, transport characteristics of pharmaceutically relevant compounds both into the body and through barrier mechanisms within the body, such as through P-glycoprotein, BCRP and multiple resistance associated proteins, both present at the blood brain barrier, the blood cerebrospinal fluid barriers and the gastrointestinal tract. Secondly, I have an interest with iron and copper related mechanisms of metabolism, and changes in tumour growth. Thirdly, Bacterial adhesion to cells expressing active efflux proteins, and fourthly, mechanisms to induce active efflux proteins in human cells. In the last decade I have focused on transport of drugs through and into Caco-2 cells and MCF7 cells. Many of my publications to date have come from the use of the Caco-2 model. One major achievement was the isolation of a potent non-transformed sub clone of Caco-2 that has expanded my ability to quantitate differences between substrates for P-gp. Work using the Caco-2 cell model to examine drug attributes for the efflux proteins currently deals with the specifics of concentration dependence, affinity, uptake characteristics, comparative rate of efflux, pH dependence, and generally exploring selected drugs in detail to estimate the implications of being a P-gp substrate in a clinical setting, using in vitro tools. This may expand to efflux protein knockout mice in the future. I have initiated Apoptosis research to look for associations between caspase 3 and 8 increases during apoptosis and P-gp over-expression. In addition, I have completed other projects aimed at identifying patients with inflammatory bowel disease at an early stage, also based on P-gp related research, and I am currently examining associations of active efflux protein expression and bacterial binding in my in vitro gut model. Recent research has focused on amphetamine derivatives, digoxin derivatives, corticosteroids and antihistamines to determining whether P-gp is responsible for inter-patient variability in patients/overdose victims. Other interests include drug discovery using natural products, in particular extracts from marine organisms that may have some benefit in cancer chemotherapy.

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Smdk, G., M. Page-Sharp, and A. Crowe. 2016.“The interactions of P-glycoprotein with antimalarial drugs, including substrate affinity, inhibition and regulation.”PLoS One 11 (4). Senarathna, K., and A. Crowe. 2015.“The influence of passage number for Caco2 cell models when evaluating P-gp mediated drug transport.”Pharmazie in Unserer Zeit 70 (12): 798-803. Omar, M. S., A. Crowe, C. Y. Tay, and J. D. Hughes. 2014.“Expressions of P-glycoprotein in treatment – Resistant Helicobacter pylori patients.”Journal of Applied Biomedicine 12 (4): 263-269. Ahmadzai, H., L. Tee, and A. Crowe. 2014.“Pharmacological role of efflux transporters: Clinical implications for medication use during breastfeeding.”World Journal of Pharmacology 3 (4): 153-161. Omar, M. S., A. Crowe, and J. D. Hughes. 2013.“Distribution of the Single Nucleotide Polymorphism C3435T of MDR1 Gene Among People in Western Australia, Australia.”International Journal of Pharmacy and Pharmaceutical Sciences 5 (4): 470-473. Crowe, A., C. Jackaman, K. M. Beddoes, B. Ricciardo, and D. J. Nelson. 2013.“Rapid Copper Acquisition by Developing Murine Mesothelioma: Decreasing Bioavailable Copper Slows Tumor Growth, Normalizes Vessels and Promotes T Cell Infiltration.”PLoS ONE 8 (8): 1-14. Crowe, A., and J. A. Keelan. 2012.“Development of a Model for Functional Studies of ABCG2 (Breast Cancer Resistance Protein) Efflux Employing a Standard BeWo Clone (B24).”Assay and Drug Development Technologies 10: 476-484. Crowe, A., and M. Bebawy. 2012.“ABCB1 (P-glycoprotein) reduces bacterial attachment to human gastointestinal LS174T epithelial cells.”European Journal of Pharmacology 689: 204-210. Omar, M. S., A. Crowe, R. W. Parsons, H. Ee, C. Y. Tay, and J. D. Hughes. 2012.“P-glycoprotein expression in Helicobacter pylori-positive patients: The influence of MDR1 C3435T polymorphism.”Journal of Digestive Diseases 13: 414-420. Crowe, A., and A. M. Tan. 2012.“Oral and inhaled corticosteroids: Differences in P-glycoprotein (ABCB1) mediated efflux.”Toxicology and Applied Pharmacology 260: 294-302. Crowe, A., and C. Wright. 2012.“The impact of P-glycoprotein mediated efflux on absorption of 11 sedating and less-sedating antihistamines using Caco-2 monolayers.”Xenobiotica 42 (6): 538-549. Crowe, A. 2011.“The role of P-glycoprotein and breast cancer resistance protein (BCRP) in bacterial attachment to human gastrointestinal cells.”Journal of Crohn's and Colitis 5 (6): 531-542. Hughes, J., and A. Crowe. 2010.“Inhibition of P-glycoprotein-mediated efflux and its metabolites by macrolide antibiotics.”Journal of Pharmacological Sciences 113: 315-324. Hughes, J., and A. Crowe. 2010.“Inhibition of P-glycoprotein-mediated efflux of digoxin and its metabolites by macrolide antibiotics.”Journal of Pharmacological Sciences 113: 315-324. Crowe, A., and S. Diep. 2008.“pH dependent efflux of methamphetamine derivatives and their reversal through human Caco-2 cell monolayers.”European Journal of Pharmacology 592 (1-3): 7-12. Crowe, A., K. F. Ilett, H. A. Karunajeewa, K. T. Batty, and T. M. Davis. 2006.“Role of P-glycoprotein in absorption of novel antimalarial drugs.”Antimicrobial Agents and Chemotherapy 50: 3504-3506. Crowe, A., and Y. K. Teoh. 2006.“Limited P-glycoprotein mediated efflux for anti-epileptic drugs.”Journal of Drug Targeting 14 (5): 291-300. Crowe, A., and P. Wong. 2004.“pH Dependent uptake of loperamide across the gastrointestinal tract: An in vitro study.”Drug Development and Industrial Pharmacy 5: 449-459. Crowe, A., and P. Wong. 2003.“Potential roles of P-gp and calcium channels in loperamide and diphenoxylate transport.”Toxicology and Applied Pharmacology 193: 127-137.