Dr Bronwyn Brown

Research Fellow
Sydney Medical School- Central
Heart Research Institute

Telephone +61 2 82088900
Fax +61 2 95655584

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Biographical details

Dr Bronwyn Brown is a Postdoctoral Research Fellow within the Inflammation Group at the Heart Research Institute (HRI), and an affiliated Research Fellow within Sydney Medical School (Central Clinical School), University of Sydney. She has a long standing interest in the role of lipoprotein modification and trafficking by macrophages during lesion development in atherosclerosis. Her PhD, awarded in 2005, was completed at the HRI under the supervision Prof Michael Davies, and focused on diabetes-associated atherosclerosis and the adverse structural and functional effects of glycation on low-density-density lipoproteins (LDL) and consequent altered macrophage function. This work led to the publication of a number of high impact original research articles, including Brown et al, Diabetologia 2005 48:361-369, and Diabetologia 2006 49:775-783. Dr Brown extended this area of research as a Postdoctoral Fellow at the HRI examining the structural and functional effects of glycation on high-density lipoproteins (HDL). She also developed expertise in assessing the role of glycation and oxidative stress in diabetes and inflammatory disease. Since joining the Inflammation Group in 2014, her research has focused on understanding how alterations to the structure, function and trafficking of LDL during chronic inflammation contributes to the development of atherosclerosis.

Current projects

THE EFFECTS OF AN INFLAMMATORY ENVIRONMENT AND MACROPHAGE PHENOTYPE ON CELLULAR TRAFFICKING OF OXIDISED LOW DENSITY LIPOPROTEINS

Supervisors

Dr Bronwyn Brown and Prof Clare Hawkins

Research Location

The Heart Research Institute, 7 Eliza Street, Newtown

Synopsis

Atherosclerosis is characterised by lipid accumulation within the intima of the artery wall and chronic inflammation, eventually leading to blockage of blood flow and clinical symptoms such as angina, heart attack or stroke. Such cardiovascular events account for 40 % of total deaths in modern developed countries. A key event in the initiation of atherosclerosis is the oxidative modification of LDL, which causes the uncontrolled cellular uptake of lipid by macrophages and triggers a cascade of inflammatory events. Myeloperoxidase (MPO) is released by activated white blood cells at sites of inflammation, including atherosclerotic lesions. It forms reactive chemical oxidants including hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN), which kill bacteria, but also damage host tissue and accelerate lesion development in atherosclerosis. HOCl and HOSCN also both modify LDL, which results in its uptake and accumulation in macrophages. In atherosclerotic lesions macrophages may be present as different phenotypes, such as pro-inflammatory (M1) or the anti-inflammatory (M2) phenotypes, depending on the microenvironment. However, there is a lack of data on how phenotypically different macrophages are affected by an MPO inflammatory environment and the subsequent consequences on cellular metabolism and LDL trafficking.

This project will focus on the effects of the MPO oxidants, HOSCN and HOCl, on phenotypically different macrophages, and how these altered inflammatory environments affect the cellular trafficking of native and oxidised LDL and macrophage metabolism. Further to this, novel antioxidants will be utilised to reverse deleterious effects. Laboratory techniques employed in this this project will include culturing human macrophages, LDL isolation and preparation, metabolic and bioenergetic techniques, flow cytometry, microscopy, Western blotting, real-time qPCR, ELISA and HPLC.

Suggested reading

[1] Stocker, R and Keaney J.F., Role of oxidative modifications in atherosclerosis. Physiol Rev 84, 1381-1478, 2004.

[2] Ismael F.O. et al., Comparative reactivity of the myeloperoxidase-derived oxidants HOCl and HOSCN with low-density lipoprotein (LDL): Implications for foam cell formation in atherosclerosis.Arch Biochem Biophys, 573, 40-51, 2015.

[3] Rayner, B.S, et al., Comparative reactivity of myeloperoxidase-derived oxidants with mammalian cells. Free Radic Biol Med, 71, 240-55, 2014.

[4] Wolfs, I.M. et al., Differentiation factors and cytokines in the atherosclerotic plaque micro-environment as a trigger for macrophage polarization. Thromb Haemost, 106, 763-771, 2011.

Associations

Australian Atherosclerosis Society (AAS)

Australian Society for Medical Research (ASMR)

Society for Redox Biology and Medicine (SFRBM)

Selected publications

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Book Chapters

  • Davies, M., Brown, B., Imran, R., van Reyk, D. (2006). The roles of protein glycation, glycoxidation and advanced glycation end-product formation in diabetes-induced atherosclerosis. In Sukhinder C. Kaur Cheema (Eds.), Biochemistry of Atherosclerosis (Advances in Biochemistry in Health and Disease), (pp. 247-283). United States: Springer Science+Business Media.

Journals

  • Ismael, F., Proudfoot, J., Brown, B., van Reyk, D., Croft, K., Davies, M., Hawkins, C. (2015). Comparative reactivity of the myeloperoxidase-derived oxidants HOCl and HOSCN with low-density lipoprotein (LDL): Implications for foam cell formation in atherosclerosis. Archives of Biochemistry and Biophysics, 573, 40-51. [More Information]
  • Brown, B., Kim, C., Torpy, F., Bursill, C., McRobb, L., Heather, A., Davies, M., van Reyk, D. (2014). Supplementation with carnosine decreases plasma triglycerides and modulates atherosclerotic plaque composition in diabetic apo E(-/-) mice. Atherosclerosis, 232(2), 403-409. [More Information]
  • Brown, B., Nobecourt, E., Zeng, J., Jenkins, A., Rye, K., Davies, M. (2013). Apolipoprotein A-I glycation by Glucose and Reactive Aldehydes Alters Phospholipid Affinity but Not Cholesterol Export from Lipid-Laden Macrophages. PloS One, 8(5), 1-9. [More Information]
  • Hadfield, K., Pattison, D., Brown, B., Hou, L., Rye, K., Davies, M., Hawkins, C. (2013). Myeloperoxidase-derived oxidants modify apolipoprotein A-I and generate dysfunctional high-density lipoproteins: comparison of hypothiocyanous acid (HOSCN) with hypochlorous acid (HOCI). The Biochemical Journal, 449(2), 531-542. [More Information]
  • Dalsgaard, T., Nielsen, J., Brown, B., Stadler, N., Davies, M. (2011). Dityrosine, 3,4-dihydroxyphenylalanine (DOPA), and radical formation from tyrosine residues on milk proteins with globular and flexible structures as a result of riboflavin-mediated photo-oxidation. Journal of Agricultural and Food Chemistry, 59(14), 7939-7947. [More Information]
  • Moheimani, F., Tan, J., Brown, B., Heather, A., van Reyk, D., Davies, M. (2011). Effect of Exposure of Human Monocyte-Derived Macrophages to High, versus Normal, Glucose on Subsequent Lipid Accumulation from Glycated and Acetylated Low-Density Lipoproteins. Experimental Diabetes Research, 2011, 1-10. [More Information]
  • Nobecourt, E., Tabet, F., Lambert, G., Puranik, R., Bao, B., Yan, L., Davies, M., Brown, B., Jenkins, A., Dusting, G., Barter, P., Rye, K., et al (2010). Nonenzymatic Glycation Impairs the Antiinflammatory Properties of Apolipoprotein A-I. Arteriosclerosis, Thrombosis, and Vascular Biology, 30(4), 766-772. [More Information]
  • Brown, B., Rashid, I., van Reyk, D., Davies, M. (2007). Glycation of low-density lipoprotein results in the time-dependent accumulation of cholesteryl esters and apolipoprotein B-100 protein in primary human monocyte-derived macrophages. The FEBS Journal, 274, 1530-1541. [More Information]
  • Nobecourt, E., Davies, M., Brown, B., Curtiss, L., Bonnet, D., Charlton, F., Januszewski, A., Jenkins, A., Barter, P., Rye, K. (2007). The impact of glycation on apolipoprotein A-I structure and its ability to activate lecithin:cholesterol acyltransferase. Diabetologia, 50(3), 643-653. [More Information]
  • Knott, H., Brown, B., Davies, M., Dean, R. (2003). Glycation and glycoxidation of low-density lipoproteins by glucose and low-molecular mass aldehydes. Formation of modified and oxidized particles. The FEBS Journal, 270(17), 3572-3582.

2015

  • Ismael, F., Proudfoot, J., Brown, B., van Reyk, D., Croft, K., Davies, M., Hawkins, C. (2015). Comparative reactivity of the myeloperoxidase-derived oxidants HOCl and HOSCN with low-density lipoprotein (LDL): Implications for foam cell formation in atherosclerosis. Archives of Biochemistry and Biophysics, 573, 40-51. [More Information]

2014

  • Brown, B., Kim, C., Torpy, F., Bursill, C., McRobb, L., Heather, A., Davies, M., van Reyk, D. (2014). Supplementation with carnosine decreases plasma triglycerides and modulates atherosclerotic plaque composition in diabetic apo E(-/-) mice. Atherosclerosis, 232(2), 403-409. [More Information]

2013

  • Brown, B., Nobecourt, E., Zeng, J., Jenkins, A., Rye, K., Davies, M. (2013). Apolipoprotein A-I glycation by Glucose and Reactive Aldehydes Alters Phospholipid Affinity but Not Cholesterol Export from Lipid-Laden Macrophages. PloS One, 8(5), 1-9. [More Information]
  • Hadfield, K., Pattison, D., Brown, B., Hou, L., Rye, K., Davies, M., Hawkins, C. (2013). Myeloperoxidase-derived oxidants modify apolipoprotein A-I and generate dysfunctional high-density lipoproteins: comparison of hypothiocyanous acid (HOSCN) with hypochlorous acid (HOCI). The Biochemical Journal, 449(2), 531-542. [More Information]

2011

  • Dalsgaard, T., Nielsen, J., Brown, B., Stadler, N., Davies, M. (2011). Dityrosine, 3,4-dihydroxyphenylalanine (DOPA), and radical formation from tyrosine residues on milk proteins with globular and flexible structures as a result of riboflavin-mediated photo-oxidation. Journal of Agricultural and Food Chemistry, 59(14), 7939-7947. [More Information]
  • Moheimani, F., Tan, J., Brown, B., Heather, A., van Reyk, D., Davies, M. (2011). Effect of Exposure of Human Monocyte-Derived Macrophages to High, versus Normal, Glucose on Subsequent Lipid Accumulation from Glycated and Acetylated Low-Density Lipoproteins. Experimental Diabetes Research, 2011, 1-10. [More Information]

2010

  • Nobecourt, E., Tabet, F., Lambert, G., Puranik, R., Bao, B., Yan, L., Davies, M., Brown, B., Jenkins, A., Dusting, G., Barter, P., Rye, K., et al (2010). Nonenzymatic Glycation Impairs the Antiinflammatory Properties of Apolipoprotein A-I. Arteriosclerosis, Thrombosis, and Vascular Biology, 30(4), 766-772. [More Information]

2007

  • Brown, B., Rashid, I., van Reyk, D., Davies, M. (2007). Glycation of low-density lipoprotein results in the time-dependent accumulation of cholesteryl esters and apolipoprotein B-100 protein in primary human monocyte-derived macrophages. The FEBS Journal, 274, 1530-1541. [More Information]
  • Nobecourt, E., Davies, M., Brown, B., Curtiss, L., Bonnet, D., Charlton, F., Januszewski, A., Jenkins, A., Barter, P., Rye, K. (2007). The impact of glycation on apolipoprotein A-I structure and its ability to activate lecithin:cholesterol acyltransferase. Diabetologia, 50(3), 643-653. [More Information]

2006

  • Davies, M., Brown, B., Imran, R., van Reyk, D. (2006). The roles of protein glycation, glycoxidation and advanced glycation end-product formation in diabetes-induced atherosclerosis. In Sukhinder C. Kaur Cheema (Eds.), Biochemistry of Atherosclerosis (Advances in Biochemistry in Health and Disease), (pp. 247-283). United States: Springer Science+Business Media.

2003

  • Knott, H., Brown, B., Davies, M., Dean, R. (2003). Glycation and glycoxidation of low-density lipoproteins by glucose and low-molecular mass aldehydes. Formation of modified and oxidized particles. The FEBS Journal, 270(17), 3572-3582.

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