Professor Andrew Brown
Research Lab, Room 256, Biological Sciences; Phone 9385-2005
- 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
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.
Honours and Awards
- Director of the Australian Society for Medical Research (2007 to present)
Active Research Projects
Zerenturk, E.J., Sharpe, L.J. & Brown, A.J. (2012)
Sterols regulate 3β-hydroxysterol Δ24-reductase (DHCR24) via dual sterol regulatory elements: Cooperative induction of key enzymes in lipid synthesis by sterol regulatory element binding proteins.
Biochimica et Biophysica acta, Molecular and Cell Biology of Lipids. 1821(10): 1350-1360.
Jansen, M., Wang, W., Greco, D., Bellenchi, G.C., Di Porzio, U., Brown, A.J. & Ikonen, E. (2012)
What dictates the accumulation of desmosterol in the developing brain?
FASEB Journal. 12(211235): 1-6.
Luu, W., Sharpe, L.J., Stevenson, J. & Brown, A.J. (2012)
Akt acutely activates the cholesterogenic transcription factor SREBP-2.
Biochimica et Biophysica acta, Molecular Cell Research. 1823(2): 458-464.
Gelissen, I.C. & Brown, A.J. (2012)
Highlights from the latest articles in statin pharmacogenomics: Predicting response to statins by pharmacogenetic testing.
Pharmacogenomics. 13(11): 1223-1225.
Burns, V., Sharpe, L.J., Gelissen, I.C. & Brown, A.J. (2012)
Species variation in ABCG1 isoform expression: Implications for the use of animal models in elucidating ABCG1 function.
Atherosclerosis. S0021-9150(12): 00870 - 00872.
Brown, A.J. (2012)
Cholesterol versus other sterols: How do they compare as physiological regulators of cholesterol homeostasis?'
European Journal of Life Science and Technology. 114(6): 617-623.
Krycer, J.R. & Brown, A.J. (2012)
Does changing androgen receptor status during prostate cancer development impact upon cholesterol homeostasis?
PLoS One. 8(1): e54007. doi:10.1371/journal.pone.0054007
Ta, M.T., Kapterian, T., Fei, W., Du, X., Brown, A.J., Dawes, I.W. & Yang, H. (2012)
Accumulation of squalene is associated with the clustering of lipid droplets.
FEBS Journal. 279(22): 4231-4244.
Sharpe, L.J., Wong, J., Garner, B., Halliday, G.M. & Brown, A.J. (2012)
Is seladin-1 really a selective Alzheimer's disease indicator?
Journal of Alzheimers Disease. 30(1): 35-39.
Zerenturk, E.J. Kristiana, I., Gill, S. & Brown, A.J., (2012)
The endogenous regulator 24(S),25-epoxycholesterol inhibits cholesterol synthesis at DHCR24 (Seladin-1).
Biochimica et Biophysica ACTA - Molecular and Cell Biology of Lipids. 1821(9): 1269-1277.
Gelissen, I.C., Sharpe, L.J., Sandoval., C., Rao, G., Kockx, M., Kritharides, L., Jessup, W., & Brown, A.J. (2012)
Protein kinase A modulates the activity of a major human isoform of ABCG1.
Journal of Lipid Research. 53(10): 2133-2140.
Kockx, M., Dinnes, D.L., Huang, K., Sharpe, L.J., Jessup, W., Brown, A.J., & Kritharides, L. (2012)
Cholesterol accumulation inhibits ER to Golgi transport and protein secretion: Studies of apolipoprotein E and VSVGt.
Biochemical Journal. 447(1): 51-60.
Kristiana, I., Luu, W., Stevenson, J., Cartland, S.P., Jessup, W., Belani, J.D., Rychnovsky, S.D., & Brown, A.J. (2012)
Cholesterol through the looking glass: Ability of its enantiomer also to elicit homeostatic responses.
The Journal of Biological Chemistry. 287(40): 33897-33904.
Krycer, J.R., Phan, L., & Brown, A.J. (2012)
A key regulator of cholesterol homoeostasis, SREBP-2, can be targeted in prostate cancer cells with natural products.
Biochemical Journal. 446(2): 191-201.
Du, X., Kazim, A., Brown, A.J., & Yang, H. (2012)
An essential role of Hrs/Vps27 in endosomal cholesterol trafficking.
Cell Reports. 1: 29-35.
Du, X., Kazim, A.S., Dawes, I.W., Brown, A.J., & Yang, H. (2012)
The AAA ATPase VPS4/SKD1 Regulates Endosomal Cholesterol Trafficking Independently of ESCRT-III.
Traffic. DOI: 10.1111/tra.12015
Eden, J.S., Sharpe, L.J., White, P.A., & Brown, A.J. (2011)
Norovirus RNA-dependent RNA polymerase is phosphorylated by an important survival kinase, Akt.
Journal of Virology. 85(20): 10894-10898.
Fei, W., Li, H., Shui, G., Kapterian, T.S., Bielby, C., Du, X., Brown, A.J., Li, P., Wenk, M.R., Liu, P., & Yang, H. (2011)
Molecular characterization of seipin and its mutants: implications for seipin in triacylglycerol synthesis.
Journal of Lipid Research. 52(12): 2136-2147.
Brown, A.J. (2011)
Isoprenoid is a perfect fit for fat factor.
Biochemical Journal. 438(1): 1-3.
Gill, S., & Brown, A.J. (2011)
Exploiting a physiological regulator to improve the efficacy and safety of statins.
Cardiovascular Drugs & Therapy. 25(2): 183-185.
Gelisson, I.C., & Brown, A.J. (2011)
Drug targets beyond HMG-CoA reductase: Why venture beyond the statins?
Frontiers In Biology. 6(3): 197-205.
Appelqvist, H., Nilsson, C., Garner, B., Brown, A.J., Kagedal, K. & Ollinger, K. (2011)
Attenuation of the lysosomal death pathway by lysosomal cholesterol accumulation.
American Journal of Pathology. 178(2): 629-639.
Du, X.R., Kumar, J., Ferguson, C., Schulz, T.A., Ong, Y.S., Hong, W., Prinz, W.A., Parton, R.G., Brown, A.J. & Yang, H. (2011)
A role for oxysterol-binding protein-related protein 5 in endosomal cholesterol trafficking.
Journal of Cell Biology. 192(1): 121-135.
Fei, W., Shui, G., Zhang, Y., Krahmer, N., Ferguson, C., Kapterian, T.S., Lin, R.C., Dawes, I.W., Brown, A.J., Li, P., Huang, X., Parton, R.G., Wenk, M.R., Walther, T.C. & Yang, H. (2011)
A role for phosphatidic acid in the formation of “supersized” lipid droplets.
PLOS Genetics. 7(7): e1002201, 1-11.
Gill, S., Stevenson, J., Kristiana, I., & Brown, A.J. (2011)
Cholesterol-dependent degradation of squalene monooxygenase, a control point in cholesterol synthesis beyond HMG-CoA reductase.
Cell Metabolism. 13(3): 260-273.
Krycer, J.R., & Brown, A.J. (2011)
Cross-talk between the androgen receptor and the liver X receptor: Implications for cholesterol homeostasis.
The Journal of Biological Chemistry. 286: 20637-20647.
Sharpe, L.J., Luu, W., & Brown, A.J. (2011)
Akt phosphorylates Sec24: New clues into the regulation of ER-to-Golgi trafficking.
Traffic (Malden). 12(1): 19-27.
Brown, A.J. & Galea, A.M. (2010)
Cholesterol as an evolutionary response to living with oxygen.
Evolution. 14(7): 2179-2183
Gelissen, I.C, Cartland, S., Brown, A.J., Sandoval, C., Kim, M., Dinnes, D.L., Lee, Y., Hsieh, V., Gaus, K., Kritharides, L. & Jessup, W. (2010)
Expression and stability of two isoforms of ABCG1 in human vascular cells.
Atherosclerosis. 208: 75–82.
Krycer, J.R., Sharpe, L.J., Luu, W. & Brown, A.J. (2010)
The Akt-SREBP nexus: Cell signaling meets lipid metabolism.
Trends in Endocrinology and Metabolism. 21: 268-278.
Wiklund, E.D., Catts, V.S., Catts, S.V., Ng, T.F., Whitaker, N.J., Brown, A.J. & Lutze-Mann, L.H. (2010)
Cytotoxic effects of antipsychotic drugs implicate cholesterol homeostasis as a novel chemotherapeutic target.
International Journal of Cancer. 126: 28-40.
Brown, A.J. (2010)
Does upsizing statins have a downside?
DrugSafety. 33: 435-436.
Brown, A.J. (2009)
24(S),25-Epoxycholesterol: A messenger for cholesterol homeostasis.
International Journal of Biochemistry and Cell Biology. 41: 744-747
Brown, A.J., Kristiana, I. & Krycer, J.R. (2009)
Cholesterol homeostasis in two commonly used human prostate cancer cell-lines, LNCap and PC-3.
PLoS ONE 4(12): e8496. (doi:10.1371/journal.pone.0008496)
Brown, A.J. & Jessup, W. (2009)
Oxysterols: Sources, cellular storage and metabolism, and new insights into their roles in cholesterol homeostasis.
Molecular Aspects of Medicine. 30: 111-122.
Galea, A.M. & Brown, A.J. (2009)
Special relationship between sterols and oxygen: Were sterols an adaptation to aerobic life?
Free Radical Biology and Medicine. 47: 880-889.
Kristiana, I., Sharpe, L.J., Catts, V.S., Lutze-Mann, L.H. & Brown A.J. (2009)
Antipsychotic drugs upregulate lipogenic gene expression by disrupting intracellular trafficking of lipoprotein-derived cholesterol.
Journal of Pharmacogenomics. 10: 396-407.
Krycer, J.R. & Brown, A.J. (2009)
Putative fat fighter hits the middle man.
Chemistry and Biology. 16: 798-800.
Stevenson, J. & Brown, A.J. (2009)
How essential is cholesterol?
Biochemical Journal. 420(2): 305-315.
Fei, W., Shui, G., Gaeta, B., Du, X., Kuerschner, L., Li, P., Brown, A.J., Wenk, M.R., Parton, R.G. & Yang, H. (2008)
Fld1p, a functional homologue of human seipin, regulates the size of lipid droplets in yeast.
Journal of Cell Biology. 180: 473-482. (Selected as an editorial highlight by JCB)
Gill S, Chow R, Brown AJ (2008)
Sterol regulators of cholesterol homeostasis and beyond: The oxysterol hypothesis revisited and revised
Progress in Lipid Research. 47: 391-404.
Wong J, Quinn CM, Gelissen IC, Brown AJ. (2008)
Endogenous 24(S),25-epoxycholesterol fine-tunes acute control of cellular cholesterol homeostasis.
The Journal of Biological Chemistry. 283:700-707.
Yan D, Mäyränpää MI, Wong J, Perttilä J, Lehto M, Jauhiainen M, Kovanen PT, Ehnholm C, Brown AJ, Olkkonen VM. (2008)
OSBP-related protein 8 (ORP8) suppresses ABCA1 expression and cholesterol efflux from macrophages.
The Journal of Biological Chemistry. 283:332-340.
Brown, A.J. (2008)
Viral hepatitis and fatty liver disease: how an unwelcome guest makes pate of the host.
The Biochemical Journal. 416: e15-17.
Kristiana, I., Yang, H.Y. and Brown, A.J. (2008)
Different kinetics of cholesterol delivery to components of the cholesterol homeostatic machinery: Implications for cholesterol trafficking to the endoplasmic reticulum.
Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids. 1781: 724-730.
McCarthy, F.R.K. and Brown, A.J. (2008)
Autonomous Hedgehog signalling is undetectable in PC-3 prostate cancer cells.
Biochemical and Biophysical Research Communications. 373: 109-112.
Sharpe, L.J. and Brown, A.J. (2008)
Rapamycin down-regulates LDL-receptor expression independently of SREBP-2.
Biochemical and Biophysical Research Communications. 373: 670-674.
Sharpe, L.J., Du, X. and Brown, A.J. (2008)
Approaches to investigate the role of signaling in ER-to-Golgi transport.
Methods in Molecular Biology. 457: 215-225.
Wong, J., Quinn, C.M., Gelissen, I.C., Jessup, W. and Brown, A.J. (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: 180-189.