个人简介
2013-current: Head of School
2013-current: Professor, School of BABS
2008-2012: Associate Professor, School of BABS
2002-2008: Senior Lecturer, School of BABS, UNSW
2000-2002: Visiting Scientist, UT Southwestern, Dallas
1994-2000: Research Scientist/Project Leader, Heart Research Institute, Sydney
研究领域
Since my undergraduate studies, my research has focused on various aspects of biochemistry involving fats (or lipids). Over the past 14 years, my focus has concentrated on one particular lipid which has become a by-word for heart disease risk, cholesterol. In fact, the cells in our body need cholesterol. However, too much cholesterol in our cells can cause disease, including heart disease. Therefore we have evolved an elaborate system for keeping the cholesterol content of our cells under tight-control.
I had the privilege to work in the laboratory of Nobel laureates, Drs Joe Goldstein and Mike Brown in Dallas, who over the past three decades have revealed layer after layer of complexity of how cells regulate their cholesterol levels. Since arriving at UNSW, I have found two important new players involved in how our cells achieve cholesterol balance. First, I discovered that our cells can make a cholesterol-like molecule that helps to control cholesterol metabolism. Second, I discovered that a critical signalling pathway, often associated with cancer, plays an important role in cholesterol metabolism.
近期论文
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Jurczyluk J; Munoz MA; Skinner OP; Chai RC; Ali N; Palendira U; Quinn JM; Preston A; Tangye SG; Brown AJ; Argent E; Ziegler JB; Mehr S; Rogers MJ, 2016, 'Mevalonate kinase deficiency leads to decreased prenylation of Rab GTPases', Immunology and Cell Biology, http://dx.doi.org/10.1038/icb.2016.58
Prabhu AV; Luu W; Sharpe LJ; Brown AJ, 2016, 'Cholesterol-mediated degradation of 7-dehydrocholesterol reductase switches the balance from cholesterol to Vitamin D synthesis', Journal of Biological Chemistry, vol. 291, no. 16, pp. 8363 - 8376, http://dx.doi.org/10.1074/jbc.M115.699546
Howe V; Sharpe LJ; Alexopoulos SJ; Kunze SV; Chua NK; Li D; Brown AJ, 2016, 'Cholesterol homeostasis: How do cells sense sterol excess?', Chemistry and Physics of Lipids, vol. 199, pp. 170 - 178, http://dx.doi.org/10.1016/j.chemphyslip.2016.02.011
Brown AJ; Hsieh J, 2016, 'Foiling IDOL to help control cholesterol', Circulation Research, vol. 118, no. 3, pp. 371 - 373, http://dx.doi.org/10.1161/CIRCRESAHA.116.308191
Loregger A; Cook ECL; Nelson JK; Moeton M; Sharpe LJ; Engberg S; Karimova M; Lambert G; Brown AJ; Zelcer N, 2016, 'A MARCH6 and IDOL E3 ubiquitin ligase circuit uncouples cholesterol synthesis from lipoprotein uptake in hepatocytes', Molecular and Cellular Biology, vol. 36, no. 2, pp. 285 - 294, http://dx.doi.org/10.1128/MCB.00890-15
Luu W; Sharpe LJ; Capell-Hattam I; Gelissen IC; Brown AJ, 2016, 'Oxysterols: Old Tale, New Twists', Annual Review of Pharmacology and Toxicology, vol. 56, pp. 447 - 467, http://dx.doi.org/10.1146/annurev-pharmtox-010715-103233
Sharpe LJ; Howe V; Prabhu AV; Luu W; Brown AJ, 2015, 'Navigating the shallows and rapids of cholesterol synthesis downstream of HMGCR', Journal of Nutritional Science and Vitaminology, vol. 61, pp. S154 - S156, http://dx.doi.org/10.3177/jnsv.61.S154
Rye KA; Barter PJ; Brown AJ, 2015, 'Speed kills in more ways than one: Methamphetamine and atherosclerosis', Atherosclerosis, vol. 243, no. 2, pp. 654 - 655, http://dx.doi.org/10.1016/j.atherosclerosis.2015.09.034
Howe V; Chua NK; Stevenson J; Brown AJ, 2015, 'The regulatory domain of squalene monooxygenase contains a re-entrant loop and senses cholesterol via a conformational change', Journal of Biological Chemistry, vol. 290, no. 46, pp. 27533 - 27544, http://dx.doi.org/10.1074/jbc.M115.675181
Aleidi SM; Howe V; Sharpe LJ; Yang A; Rao G; Brown AJ; Gelissen IC, 2015, 'The E3 ubiquitin ligases, HUWE1 and NEDD4-1, are involved in the post-translational regulation of the ABCG1 and ABCG4 lipid transporters', Journal of Biological Chemistry, vol. 290, no. 40, pp. 24604 - 24613, http://dx.doi.org/10.1074/jbc.M115.675579
Du X; Zhang Y; Jo SR; Liu X; Qi Y; Osborne B; Byrne FL; Smith GC; Turner N; Hoehn KL; Brown AJ; Yang H, 2015, 'Akt activation increases cellular cholesterol by promoting the proteasomal degradation of Niemann-Pick C1', Biochemical Journal, vol. 471, no. 2, pp. 243 - 253, http://dx.doi.org/10.1042/BJ20150602
Stevenson J; Brown AJ, 2015, 'Universal CG cloning of polymerase chain reaction products', Analytical Biochemistry, vol. 471, pp. 80 - 82, http://dx.doi.org/10.1016/j.ab.2014.10.018
Sharpe LJ; Rao G; Jones PM; Glancey E; Aleidi SM; George AM; Brown AJ; Gelissen IC, 2015, 'Cholesterol sensing by the ABCG1 lipid transporter: Requirement of a CRAC motif in the final transmembrane domain', Biochimica et Biophysica Acta: international journal of biochemistry and biophysics, vol. 1851, no. 7, pp. 956 - 964, http://dx.doi.org/10.1016/j.bbalip.2015.02.016
Moon H; Ruelcke JE; Choi E; Sharpe LJ; Nassar ZD; Bielefeldt-Ohmann H; Parat MO; Shah A; Francois M; Inder KL; Brown AJ; Russell PJ; Parton RG; Hill MM, 2015, 'Diet-induced hypercholesterolemia promotes androgen-independent prostate cancer metastasis via IQGAP1 and caveolin-1', Oncotarget, vol. 6, no. 10, pp. 7438 - 7453
Du X; Brown AJ; Yang H, 2015, 'Novel mechanisms of intracellular cholesterol transport: Oxysterol-binding proteins and membrane contact sites', Current Opinion in Cell Biology, vol. 35, pp. 37 - 42, http://dx.doi.org/10.1016/j.ceb.2015.04.002
Luu W; Hart-Smith G; Sharpe LJ; Brown AJ, 2015, 'The terminal enzymes of cholesterol synthesis, DHCR24 and DHCR7, interact physically and functionally', Journal of Lipid Research, vol. 56, no. 4, pp. 888 - 897, http://dx.doi.org/10.1194/jlr.M056986
Sharpe LJ; Cook ECL; Zelcer N; Brown AJ, 2014, 'The UPS and downs of cholesterol homeostasis', Trends in Biochemical Sciences, vol. 39, no. 11, pp. 527 - 535, http://dx.doi.org/10.1016/j.tibs.2014.08.008
Meerman R; Brown AJ, 2014, 'When somebody loses weight, where does the fat go?', British Medical Journal, vol. 349, http://dx.doi.org/10.1136/bmj.g7257
Prabhu AV; Sharpe LJ; Brown AJ, 2014, 'The sterol-based transcriptional control of human 7-dehydrocholesterol reductase (DHCR7): Evidence of a cooperative regulatory program in cholesterol synthesis', BBA: Molecular and Cell Biology of Lipids, vol. 1841, no. 10, pp. 1431 - 1439, http://dx.doi.org/10.1016/j.bbalip.2014.07.006
Stevenson J; Luu W; Kristiana I; Brown AJ, 2014, 'Squalene mono-oxygenase, a key enzyme in cholesterol synthesis, is stabilized by unsaturated fatty acids', Biochemical Journal, vol. 461, no. 3, pp. 435 - 442, http://dx.doi.org/10.1042/BJ20131404