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The role of ABC-lipid transporters in health and disease. ABC-transporters are membrane proteins involved in the translocation of substrates across cellular membranes. A number of lipid transporters, including ABCA1 and ABCG1, are involved in removing cholesterol from cells, a process that is important in the maintenance of cellular cholesterol homeostasis. Disregulation of cholesterol homeostasis is of interest to a number of diseases including atherosclerosis, which causes cardiovascular disease and neurogenerative diseases. The basic mechanisms by which these transporters operate is poorly understood, as is their post-translational regulation. These aspects are under investigation in our lab. • The use of cholesterol-lowering mediation in children and adolescents (collaboration with Dr Rebekah Moles and Associate Professor Parisa Aslani). The statins has been used successfully in adults for the treatment of high plasma cholesterol. Children and adolescents can also have high cholesterol levels, due to genetic factors such as Familial Hypercholesterolemia (FH), lifestyle factors such as obesity or medication use. There are currently no guidelines available for the use of statins in children and adolescents other than those with FH. We are currently performing audits in children’s hospitals in Australia in order to get a better understanding of the use of statins in the paediatric setting.

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Rumzhum, N., Patel, B., Prabhala, P., Gelissen, I., Oliver, B., Ammit, A. (2016). IL-17A increases TNF-α-induced COX-2 protein stability and augments PGE2 secretion from airway smooth muscle cells: impact on β2 -adrenergic receptor desensitization. Allergy, 71(3), 387-396. [More Information] Sharpe, L., Rao, G., Jones, P., Glancey, E., Aleidi, S., George, A., Brown, A., Gelissen, I. (2015). Cholesterol sensing by the ABCG1 lipid transporter: Requirement of a CRAC motif in the final transmembrane domain. Biochimica et Biophysica Acta. Molecular and Cell Biology of Lipids, 1851 (7), 956-964. [More Information] Aleidi, S., Howe, V., Sharpe, L., Yang, A., Rao, G., Brown, A., Gelissen, I. (2015). The E3 Ubiquitin Ligases, HUWE1 and NEDD4-1, Are Involved in the Post-translational Regulation of the ABCG1 and ABCG4 Lipid Transporters. The Journal of Biological Chemistry, 290(40), 24604-24613. [More Information] Olivier, M., Bott, R., Frisdal, E., Nowicki, M., Plengpanich, W., Desmarchelier, C., Roi, S., Quinn, C., Gelissen, I., Jessup, W., et al (2014). ABCG1 is involved in vitamin e efflux. Biochimica et Biophysica Acta. Molecular and Cell Biology of Lipids, 1841 (12), 1741-1751. [More Information] Hsieh, V., Kim, M., Gelissen, I., Brown, A., Sandoval, C., Hallab, J., Kockx, M., Traini, M., Jessup, W., Kritharides, L. (2014). Cellular Cholesterol Regulates Ubiquitination and Degradation of the Cholesterol Export Proteins ABCA1 and ABCG1. The Journal of Biological Chemistry, 289(11), 7524-7536. [More Information] Gelissen, I., Nguyen, H., Tiao, D., Ayoub, R., Aslani, P., Moles, R. (2014). Statin Use in Australian Children: A Retrospective Audit of Four Pediatric Hospitals. Pediatric Drugs, 16(5), 417-423. [More Information] Gelissen, I., McLachlan, A. (2014). The Pharmacogenomics of Statins. Pharmacological Research, 88, 99-106. [More Information] Burns, V., Sharpe, L., Gelissen, I., Brown, A. (2013). Species variation in ABCG1 isoform expression: Implications for the use of animal models in elucidating ABCG1 function. Atherosclerosis, 226(2), 408-411. [More Information] Luu, W., Sharpe, L., Gelissen, I., Brown, A. (2013). The Role of Signalling in Cellular Cholesterol Homeostasis. IUBMB Life, 65(8), 675-684. [More Information] Gelissen, I., Brown, A. (2012). Predicting response to statins by pharmacogenetic testing. Pharmacogenomics, 13(11), 1223-1225. [More Information] Gelissen, I., Sharpe, L., Sandoval, C., Rao, G., Kockx, M., Kritharides, L., Jessup, W., Brown, A. (2012). Protein kinase A modulates the activity of a major human isoform of ABCG1. Journal of Lipid Research, 53(10), 2133-2140. [More Information] Gelissen, I., Brown, A. (2011). Drug targets beyond HMG-CoA reductase: Why venture beyond the statins? Frontiers in Biology, 6(3), 197-205. [More Information] Kerr, I., Haider, A., Gelissen, I. (2011). The ABCG family of membrane-associated transporters: you don't have to be big to be mighty. British Journal of Pharmacology, 164(7), 1767-1779. [More Information] Calabresi, L., Favari, E., Moleri, E., Adorni, M., Pedrelli, M., Costa, S., Jessup, W., Gelissen, I., Kovanen, P., Bernini, F., et al (2009). Functional LCAT is not required for macrophage cholesterol efflux to human serum. Atherosclerosis, 204, 141-146. [More Information] Out, R., Jessup, W., Le Goff, W., Hoekstra, M., Gelissen, I., Zhao, Y., Kritharides, L., Chimini, G., Kuiper, J., Chapman, M., et al (2008). Coexistence of foam cells and hypocholesterolemia in mice lacking the ABC transporter A1 and G1. Circulation Research, 102, 113-120. [More Information] Wong, J., Quinn, C., Gelissen, I., Jessup, W., Brown, A. (2008). The effect of statins on ABCA1 and ABCG1 expression in human macrophages is influenced by cellular cholesterol levels and extent of differentiation. Atherosclerosis, 196(1), 180-189. [More Information] Wong, J., Quinn, C., Gelissen, I., Brown, A. (2007). Endogenous 24(S),25-Epoxycholesterol Fine-tunes Acute Control of Cellular Cholesterol Homeostasis. Journal of Biological Chemistry, 283, 700-707. Kim, W., Rahmanto, A., Kamili, A., Rye, K., Guillemin, G., Gelissen, I., Jessup, W., Hill, A., Garner, B. (2007). Role of ABCG1 and ABCA1 in Regulation of Neuronal Cholesterol Efflux to Apolipoprotein E Discs and Suppression of Amyloid- Peptide Generation. Journal of Biological Chemistry, 282, 2851-2861. Glaros, E., Kim, W., Quinn, C., Wong, J., Gelissen, I., Jessup, W., Garner, B. (2005). Glycosphingolipid accumulation inhibits cholesterol efflux via the ABCA1/apolipoprotein A-I pathway: 1-phenyl-2-decanoylamino-3-morpholino-1-propanol is a novel cholesterol efflux accelerator. Journal of Biological Chemistry, 280, 24515-24523.

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