School of Biological Sciences

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Brett Garner

Professor
ARC Future Fellow
NHMRC Senior Research Fellow (Honorary)

32.306
+61 2 4298 1576
Fax: +61 2 4221 8130
Email: brettg@uow.edu.au

Research Interests

Lipid homeostasis in the brain
Apolipoprotein structure and function
Lysosome biology
ATP-binding cassette transporter function in the brain
Therapeutic targeting sphingolipid metabolism
Oxidative stress and lipid peroxidation
Ageing
Neurodegeneration
Alzheimer’s disease
Parkinson’s disease

The Garner Group is located in the Illawarra Health and Medical Research Institute (IHMRI) in new laboratories that are well equipped for cell and molecular biology, analytical biochemistry, advanced microscopy and animal studies. A major goal of Prof Garner's group is to understand the regulation of brain lipid homeostasis and how this contributes to neurodegeneration. A strong emphasis is placed on the identification of novel therapeutic targets that modulate lipid parameters and oxidative stress with an ultimate goal to treat neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease. An overview of current research projects is provided below.

Garner Group Members (March 2012)

Dr Henry Li (Research Fellow, Laboratory Manager)

Dr Sarah Abbott (Associate Research Fellow)

Ms Kalani Ruberu (Research Assistant)

Ms Adena Spiro (Research Assistant)

Ms Shan Kornfeld (PhD Student)

Mr Peter Zhao (PhD Student)

Ms Surabhi Bhatia (PhD Student, NeuRA)

Dr Andrew Jenner (Senior Research Fellow)

Mr Fabian Kreilaus (PhD Student, primary supervisor Andrew Jenner)

Representative Publications

Selected peer-reviewed publications in chronological order.

1. Christen S, Thomas SR, Garner B, Stocker R (1994) Inhibition by interferon-gamma of human mononuclear cell-mediated low density lipoprotein oxidation. Participation of tryptophan metabolism along the kynurenine pathway. J Clin Invest 93: 2149-2158.

2. Garner B, Dean RT, Jessup W (1994) Human macrophage-mediated oxidation of low-density lipoprotein is delayed and independent of superoxide production. Biochem J 301: 421-428.

3. Garner B, Jessup W (1996) Cell-mediated oxidation of low-density lipoprotein: the elusive mechanism(s). Redox Rep 2: 97-104.

4. Garner B, Baoutina A, Dean RT, Jessup W (1997) Regulation of serum-induced lipid accumulation in human monocyte- derived macrophages by interferon-gamma. Correlations with apolipoprotein E production, lipoprotein lipase activity and LDL receptor-related protein expression. Atherosclerosis 128: 47-58.

5. Garner B, Li W, Roberg K, Brunk UT (1997) On the cytoprotective role of ferritin in macrophages and its ability to enhance lysosomal stability. Free Radic Res 27: 487-500.

6. Garner B, van Reyk D, Dean RT, Jessup W (1997) Direct copper reduction by macrophages. Its role in low density lipoprotein oxidation. J Biol Chem 272: 6927-6935.

7. Garner B, Roberg K, Brunk UT (1998) Endogenous ferritin protects cells with iron-laden lysosomes against oxidative stress. Free Radic Res 29: 103-114.

8. Garner B, Waldeck AR, Witting PK, Rye KA, Stocker R (1998) Oxidation of high density lipoproteins II. Evidence for direct reduction of lipid hydroperoxides by methionine residues of apolipoproteins AI and AII. J Biol Chem 273: 6088-6095.

9. Garner B, Witting PK, Waldeck AR, Christison JK, Raftery M, Stocker R (1998) Oxidation of high density lipoproteins I. Formation of methionine sulfoxide in apolipoproteins AI and AII is an early event that accompanies lipid peroxidation and can be enhanced by alpha-tocopherol. J Biol Chem 273: 6080-6087.

10. Garner B, Georgevich A, Hodgson AJ, Liu L, Wallace GG (1999) Polypyrrole-heparin composites as stimulus-responsive substrates for endothelial cell growth. J Biomed Mater Res 44: 121-129.

11. Garner B, Roberg K, Qian M, Brunk UT, Eaton JW, Truscott RJ (1999) Redox availability of lens iron and copper: implications for HO• generation in cataract. Redox Rep 4: 313-315.

12. Garner B, Vazquez S, Griffith R, Lindner RA, Carver JA, Truscott RJ (1999) Identification of glutathionyl-3-hydroxykynurenine glucoside as a novel fluorophore associated with aging of the human lens. J Biol Chem 274: 20847-20854.

13. Garner B, Wallace GG, Hodgson AJ, Underwood PA (1999) Human endothelial cell attachment to and growth on polypyrrole-heparin is vitronectin dependent. J Mater Sci Mater Med 10: 19-27.

14. Hood BD, Garner B, Truscott RJ (1999) Human lens coloration and aging. Evidence for crystallin modification by the major ultraviolet filter, 3-hydroxy-kynurenine O-beta-D- glucoside. J Biol Chem 274: 32547-32550.

15. Garner B, Davies MJ, Truscott RJ (2000) Formation of hydroxyl radicals in the human lens is related to the severity of nuclear cataract. Exp Eye Res 70: 81-88.

16. Garner B, Roberg K, Qian M, Eaton JW, Truscott RJ (2000) Distribution of ferritin and redox-active transition metals in normal and cataractous human lenses [In Process Citation]. Exp Eye Res 71: 599-607.

17. Garner B, Shaw DC, Lindner RA, Carver JA, Truscott RJ (2000) Non-oxidative modification of lens crystallins by kynurenine: a novel post-translational protein modification with possible relevance to ageing and cataract. Biochim Biophys Acta 1476: 265-278.

18. Vazquez S, Garner B, Sheil MM, Truscott RJ (2000) Characterisation of the major autoxidation products of 3- hydroxykynurenine under physiological conditions. Free Radic Res 32: 11-23.

19. Garner B, Harvey DJ, Frischmann M, Nigon F, Chapman MJ, Rudd PM (2001) Human apolipoprotein B-100 oligosaccharide structure is not altered in familial hypercholesterolaemia or non insulin dependent diabetes. Atherosclerosis (suppl) 2: 43-44.

20. Garner B, Harvey DJ, Royle L, Frischmann M, Nigon F, Chapman MJ, Rudd PM (2001) Characterisation of human apolipoprotein B100 oligosaccharides in low density lipoprotein (LDL) subfractions derived from normal and hyperlipidemic plasma. Deficiency of a-N-acetylneuraminyllactosyl ceramide in light and small dense LDL. Glycobiology 11: 791-802.

21. Garner B, Merry AH, Royle L, Harvey DJ, Rudd PM, Thillet J (2001) Structural elucidation of the N- and O-glycans of human apolipoprotein (a). Role of O-glycans in conferring protease resistance. J Biol Chem 276: 22200-22208.

22. Garner B, Merry AH, Royle L, Harvey DJ, Rudd PM, Thillet J (2001) Characterisation of the N- and O-glycans of apolipoprotein(a) and their role in conferring protease resistance. Glycoconjugate J 18: 47.

23. Wing DR, Garner B, Hunnam V, Reinkensmeier G, Andersson U, Harvey DJ, Dwek RA, Platt FM, Butters TD (2001) High-performance liquid chromatography analysis of ganglioside carbohydrates at the pmol level after ceramide glycanse digestion and fluorescent labelling with 2-aminobenzamide. Anal Biochem 298: 207-217.

24. Garner B, Mellor HR, Butters TD, Dwek RA, Platt FM (2002) Modulation of THP-1 macrophage and cholesterol-loaded foam cell apolipoprotein-E levels by glycosphingolipids. Biochem Biophys Res Commun 290: 1361-1367.

25. Garner B, Priestman DA, Stocker R, Harvey DJ, Butters TD, Platt FM (2002) Increased glycosphingolipid levels in serum and aortae of apolipoprotein E gene knockout mice. J Lipid Res 43: 205-214.

26. Garner B (2003) Apolipoprotein glycosylation and its potential influence in atherogenesis. Glycobiology 18: 865.

27. Garner B, Nigon F, Chapman MJ, Harvey DJ, Rudd PM (2003) Structural analysis of apoB100 oligosaccharides from LDL subpopulations in normal an hypercholesterolaemic subjects: Implications for the desialylated LDL hypothesis. Clin Exp Pharmacol P 30: 17.

28. Quinn CM, Kagedal K, Terman A, Stroikin U, Brunk UT, Jessup W, Garner B (2004) Induction of fibroblast apolipoprotein E expression during apoptosis, starvation-induced growth arrest and mitosis. Biochem J 378: 753-761.

29. Tedla N, Glaros EN, Brunk UT, Jessup W, Garner B (2004) Heterogeneous expression of apolipoprotein-E by human macrophages. Immunology 113: 338-347.

30. Fedorow H, Pickford R, Hook JM, Double KL, Halliday GM, Gerlach M, Riederer P, Garner B (2005) Dolichol is the major lipid component of human substantia nigra neuromelanin. J Neurochem 92: 990-995.

31. Glaros EN, Kim WS, Quinn CM, Wong J, Gelissen I, Jessup W, Garner B (2005) Glycosphingolipid accumulation inhibits cholesterol efflux via the ABCA1 / apoA-I pathway. 1-Phenyl-2-Decanoylamino-3-Morpholino-1-Propanol is a novel cholesterol efflux accelerator. J Biol Chem 280: 24515-24523.

32. Raftery M, Campbell R, Glaros EN, Rye KA, Halliday GM, Jessup W, Garner B (2005) Phosphorylation of Apolipoprotein-E at an Atypical Protein Kinase CK2 PSD/E Site in Vitro. Biochemistry 44: 7346-7353.

33. Fedorow H, Pickford R, Kettle E, Cartwright M, Halliday GM, Gerlach M, Riederer P, Garner B, Double KL (2006) Investigation of the lipid component of neuromelanin. J Neural Transm 113: 735-739.

34. He Z, Aristoteli LP, Kritharides L, Garner B (2006) HPLC analysis of discrete haptoglobin isoform N-linked oligosaccharides following 2D-PAGE isolation. Biochem Biophys Res Commun 343: 496-503.

35. Kim WS, Chalfant CE, Garner B (2006) Fine tuning therapeutic targeting of the sphingolipid biosynthetic pathway to treat atherosclerosis. Curr Vasc Pharmacol 4: 151-154.

36. Kim WS, Guillemin GJ, Glaros EN, Lim CK, Garner B (2006) Quantitation of ATP-binding cassette subfamily-A transporter gene expression in primary human brain cells. Neuroreport 17: 891-896.

37. Broer S, Broer A, Hansen JT, Bubb WA, Balcar VJ, Nasrallah FA, Garner B, Rae C (2007) Alanine metabolism, transport, and cycling in the brain. J Neurochem 102: 1758-1770.

38. Dedov VN, Griffiths FM, Garner B, Halliday GM, Double KL (2007) Lipid content determines aggregation of neuromelanin granules in vitro. J Neural Transm Suppl 72: 35-38.

39. Elliott DA, Kim WS, Jans DA, Garner B (2007) Apoptosis induces neuronal apolipoprotein-E synthesis and localization in apoptotic bodies. Neurosci Lett 416: 206-210.

40. Glaros EN, Kim WS, Wu BJ, Suarna C, Quinn CM, Rye KA, Stocker R, Jessup W, Garner B (2007) Inhibition of atherosclerosis by the serine palmitoyl transferase inhibitor myriocin is associated with reduced plasma glycosphingolipid concentration. Biochem Pharmacol 73: 1340-1346.

41. Guillemin GJ, Cullen KM, Lim CK, Smythe GA, Garner B, Kapoor V, Takikawa O, Brew BJ (2007) Characterization of the kynurenine pathway in human neurons. J Neurosci 27: 12884-12892.

42. Kim WS, Suryo Rahmanto A, Kamili A, Rye KA, Guillemin GJ, Gelissen IC, Jessup W, Hill AF, Garner B (2007) Role of ABCG1 and ABCA1 in regulation of neuronal cholesterol efflux to apolipoprotein-E discs and suppression of amyloid-beta peptide generation. J Biol Chem 282: 2851-2861.

43. Chan SL, Kim WS, Kwok JB, Hill AF, Cappai R, Rye KA, Garner B (2008) ATP-binding cassette transporter A7 regulates processing of amyloid precursor protein in vitro. J Neurochem 106: 793-804.

44. Cheng D, Kim WS, Garner B (2008) Regulation of alpha-synuclein expression by liver X receptor ligands in vitro. Neuroreport 19: 1685-1689.

45. Double KL, Dedov VN, Fedorow H, Kettle E, Halliday GM, Garner B, Brunk UT (2008) The comparative biology of neuromelanin and lipofuscin in the human brain. Cell Mol Life Sci 65: 1669-1682.

46. Elliott DA, Kim WS, Jans DA, Garner B (2008) Macrophage apolipoprotein-E knockdown modulates caspase-3 activation without altering sensitivity to apoptosis. Biochim Biophys Acta 1780: 145-153.

47. Garner B (2008) Myriocin as an atherosclerosis inhibitor. Future Lipidol 3: 221-224.

48. Glaros EN, Kim WS, Quinn CM, Jessup W, Rye KA, Garner B (2008) Myriocin slows the progression of established atherosclerotic lesions in apolipoprotein E gene knockout mice. J Lipid Res 49: 324-331.

49. Glaros EN, Kim WS, Rye KA, Shayman JA, Garner B (2008) Reduction of plasma glycosphingolipid levels has no impact on atherosclerosis in apolipoprotein E-null mice. J Lipid Res 49: 1677-1681.

50. Kim WS, Elliott DA, Kockx M, Kritharides L, Rye KA, Jans DA, Garner B (2008) Analysis of apolipoprotein E nuclear localization using green fluorescent protein and biotinylation approaches. Biochem J 409: 701-709.

51. Kim WS, Hill AF, Garner B (2008) Impact of human neuronal ABC transporters on cholesterol efflux and amyloid-beta production. New Trends in Alzheimer and Parkinson Related Disorders. Pianoro: Medimond. pp. 43 - 48.

52. Kim WS, Weickert CS, Garner B (2008) Role of ATP-binding cassette transporters in brain lipid transport and neurological disease. J Neurochem 104: 1145-1166.

53. Nasrallah FA, Garner B, Ball GE, Rae C (2008) Modulation of brain metabolism by very low concentrations of the commonly used drug delivery vehicle dimethyl sulfoxide (DMSO). J Neurosci Res 86: 208-214.

54. Kim WS, Chan SL, Hill AF, Guillemin GJ, Garner B (2009) Impact of 27-Hydroxycholesterol on Amyloid-beta Peptide Production and ATP-Binding Cassette Transporter Expression in Primary Human Neurons. J Alzheimers Dis 16: 121-131.

55. Kim WS, Wong J, Weickert CS, Webster MJ, Bahn S, Garner B (2009) Apolipoprotein-D expression is increased during development and maturation of the human prefrontal cortex. J Neurochem 109: 1053-1066.

56. Chen Y, Stankovic R, Cullen KM, Meininger V, Garner B, Coggan S, Grant R, Brew BJ, Guillemin GJ (2010) The kynurenine pathway and inflammation in amyotrophic lateral sclerosis. Neurotox Res 18: 132-142.

57. Elliott DA, Halliday GM, Garner B (2010) Apolipoprotein-E forms dimers in human frontal cortex and hippocampus. BMC Neurosci 11: 23.

58. Elliott DA, Weickert CS, Garner B (2010) Apolipoproteins in the brain – implications for neurological and psychiatric disorders. Clin Lipidol 5: 555-573.

59. Garner B (2010) Lipids and Alzheimer's disease. Biochim Biophys Acta 1801: 747-749.

60. Glaros EN, Kim WS, Garner B (2010) Myriocin-mediated up-regulation of hepatocyte apoA-I synthesis is associated with ERK inhibition. Clin Sci (Lond) 118: 727-736.

61. Kagedal K, Kim WS, Appelqvist H, Chan S, Cheng D, Agholme L, Barnham K, McCann H, Halliday G, Garner B (2010) Increased expression of the lysosomal cholesterol transporter NPC1 in Alzheimer's disease. Biochim Biophys Acta 1801: 831-838.

62. Kim WS, Bhatia S, Elliott DA, Agholme L, Kagedal K, McCann H, Halliday GM, Barnham KJ, Garner B (2010) Increased ATP-binding cassette transporter A1 expression in Alzheimer's disease hippocampal neurons. J Alzheimers Dis 21: 193-205.

63. Li H, Kim WS, Guilemin GJ, Hill AF, Evin G, Garner B (2010) Modulation of amyloid precursor protein processing by synthetic ceramide analogues. Biochim Biophys Acta 1801: 887-895.

64. Piguet O, Garner B (2010) Vascular pharmacotherapy and dementia. Curr Vasc Pharmacol 8: 44-50.

65. Appelqvist H, Nilsson C, Garner B, Brown AJ, Kagedal K, Ollinger K (2011) Attenuation of the lysosomal death pathway by lysosomal cholesterol accumulation. Am J Pathol 178: 629-639.

66. Cheng D, Jenner AM, Shui G, Cheong WF, Mitchell TW, Nealon JR, Kim WS, McCann H, Wenk MR, Halliday GM, Garner B (2011) Lipid pathway alterations in Parkinson's disease primary visual cortex. PLoS One 6: e17299.

67. Elliott DA, Tsoi K, Holinkova S, Chan SL, Kim WS, Halliday GM, Rye KA, Garner B (2011) Isoform-specific proteolysis of apolipoprotein-E in the brain. Neurobiol Aging 32: 257-271.

68. Hejazi L, Wong JW, Cheng D, Proschogo N, Ebrahimi D, Garner B, Don AS (2011) Mass and Relative Elution Time Profiling: Two-dimensional Analysis of Sphingolipids in Alzheimer's Disease Brains. Biochem J 438: 165-175.

69. Kim WS, Hill AF, Fitzgerald ML, Freeman MW, Evin G, Garner B (2011) Wild type and Tangier disease ABCA1 mutants modulate cellular amyloid-beta production independent of cholesterol efflux activity. J Alzheimers Dis 27: 441-452.

70. Zhao H, Brunk UT, Garner B (2011) Age-related lysosomal dysfunction: an unrecognized roadblock for cobalamin trafficking? Cell Mol Life Sci 68: 3963-3969.

71. Bhatia S, Knoch B, Wong J, Kim WS, Else PL, Oakley AJ, Garner B (2012) Selective reduction of hydroperoxyeicosatetraenoic acids to their hydroxy derivatives by apolipoprotein-D: Implications for lipid antioxidant activity and Alzheimer's disease. Biochem J 442: 713-721.

72. Karl T, Bhatia S, Cheng D, Kim WS, Garner B (2012) Cognitive phenotyping of amyloid precursor protein transgenic J20 mice. Behav Brain Res 228: 392-397.

73. Li H, Evin G, Hill AF, Hung YH, Bush AI, Garner B (2012) Dissociation of ERK signalling inhibition from the anti-amyloidogenic action of synthetic ceramide analogues. Clin Sci (Lond) 122: 409-419.

74. Sharpe LJ, Wong J, Garner B, Halliday GM, Brown AJ (2012) Is Seladin-1 really a selective Alzheimer’s disease indicator? J Alzheimers Dis: DOI 10.3233/JAD-2012-111955.

75. Wong J, Garner B (2012) Evidence that truncated TrkB isoform, TrkB-Shc can regulate phosphorylated TrkB protein levels. Biochem Biophys Res Commun: DOI 10.1016/j.bbrc.2012.02.159.

76. Wong J, Higgins M, Romeo T, Halliday GM, Garner B (2012) Amyloid beta selectively modulates neuronal TrkB alternative transcript expression with implications for Alzheimer's disease. Neuroscience: DOI 10.1016/j.neuroscience.2012.02.037.

77. Karl T, Cheng D, Garner B, Arnold JC (2012) The therapeutic potential of the endocannabinoid system for Alzheimer’s disease. Expert Opin Ther Targets: DOI 10.1517/14728222.2012.671812.

78. Oakley AJ, Bhatia S, Ecroyd H, Garner B (2012) Molecular dynamics analysis of apolipoprotein-D - lipid hydroperoxide interactions: mechanism for selective oxidation of Met-93. PLoS ONE: 7: e34057

Current Projects

Lipid antioxidant function of apoD

Apolipoprotein-D (apoD) is a member of the lipocalin family that is associated with lipid antioxidant action in the brain. We have recently identified a contributing mechanism underlying this antioxidant action that relies on one specific methionine residue. We are currently studying the antioxidant function of apoD in Alzheimer’s disease. This project is in collaboration with Dr Tim Karl, Neuroscience Research Australia and Dr Aaron Oakley, UOW.

Age-related lysosomal dysfunction

We have recently put forward a new hypothesis suggesting that lysosomal dysfunction associated with ageing and neurodegenerative diseases, such as Alzheimer’s disease, may prevent the cellular utilization of vitamin-B12. This could result in accumulation of toxic species such as homocysteine and methyl malonic acid in the brain and in this way contribute to neuron death. In related work on lysosome biology, we are investigating the impact that ABC transporters and a lysosomal cholesterol transporter NPC1 have on lysosomal membrane lipid composition, APP processing and amyloid-beta production. These projects are in collaboration with Prof Ulf Brunk and Dr Katarina Kågedal, University of Linköping, Sweden.

Role of cholesterol and sphingolipids in neuronal amyloid-beta peptide formation and Alzheimer’s disease

Our work has shown that cellular glycosphingolipid (GSL) accumulation promotes cholesterol storage. We also discovered that the GSL synthesis inhibitor D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) dose-dependently stimulates cholesterol removal from human cells. Other work has shown that the formation of neurotoxic amyloid-beta peptides is regulated by cellular cholesterol and GSL concentration and specifically by the lipid composition of cell membrane microdomains know as lipid rafts. We are studying the key cellular pathways responsible for regulating neuronal lipid raft composition in order to develop novel therapeutic strategies to inhibit the formation of amyloid-beta peptides. We are also investigating how sphingolipid metabolism may be altered in Alzheimer’s disease. This may in the future offer novel treatment options for Alzheimer's disease. This project is in collaboration with Dr Genevieve Evin, University of Melbourne; Dr Andrew Jenner, UOW and Dr Anthony Don, University of New South Wales.

Regulation of neuronal cholesterol balance and amyloid-beta production by ATP-binding cassette (ABC) transporters

We have shown that specific ATP-binding cassette (ABC) transporter subfamily A and subfamily G members are expressed in human neurons and other brain cells. We are undertaking a detailed analysis of the function of these transporters in the brain with a focus on the control of lipid homeostasis and amyloid-beta production. We propose that neuronal ABC transporters are crucial regulators of lipid balance and may therefore modulate pathways contributing to neurodegeneration and Alzheimer's disease. Our current studies focus on identifying which of the ABC transporters are involved in the regulation of neuronal cholesterol efflux to apolipoprotein-E (a key cholesterol transport protein in the brain) as well as the impact of specific transporters on amyloid-beta production in the brain. This work utilises cellular and molecular research as well as in vivo mouse studies. In the latter studies we are examining the role of specific ABC transporters in the deposition of amyloid-beta in the brain. In order to achieve this we are crossing transgenic mice that express the human amyloid precursor protein (APP) with the Swedish and Indiana familial Alzheimer's disease mutations with specific ABC transporter gene knock-out mice.

Understanding the function of apolipoprotein-E in neurobiology and neurodegeneration

ApoE plays an important role in brain lipid transport and neurodegenerative disease, however, the intracellular mechanisms involved are unclear. We have a focus on the post-translational modifications and cellular trafficking and expression of apoE. We have shown that apoE can be phosphorylated and that its expression is transcriptionally up-regulated in neurons and other cell types under apoptotic and senescence-related in vitro conditions. We found that an atypical PSD/E protein kinase CK2 phosphorylation site at the apoE C-terminus is also present in the C-terminus of alpha-synuclein, another protein that plays a role in neurodegenerative disease. Phosphorylation of this specific C-terminal site in alpha-synuclein is a critical determinant of its neuropathogenic associations and similar modifications in apoE could contribute to neurodegeneration. We have also discovered that apoE may be translocated to the nucleus in specific cell types and that it is proteolytically cleaved in the human brain. This project is providing a detailed analysis of human brain apoE post-translational modifications and mechanistic details of the potential regulation of neuronal cholesterol efflux. Our current objectives are to characterise the intracellular trafficking pathways of apoE, determine the potential function of nuclear apoE through binding partner studies and define the pathways that result in apoE fragmentation in the brain.

Regulation of lipid metabolism in Parkinson’s disease

Lewy bodies are neuropathological inclusions found in Parkinson's disease brain and are composed of aggregated proteins including alpha-synuclein and other components including lipids. Alpha-synuclein is a 14 kDa neuronal protein that is found natively in its monomeric form but undergoes aggregation in neurodegenerative diseases. While its exact function is unknown, alpha-synuclein binds phospholipids, fatty acids, and cholesterol which has raised the question as to whether alpha-synuclein can be considered as a specialised apolipoprotein. Previous work has shown that increased cellular alpha-synuclein predisposes towards aggregation and neurodegeneration, however, very little is known regarding the regulation of alpha-synuclein gene expression in the brain and how this is related to lipid homeostasis. Our current studies are focused on understanding the mechanisms controlling alpha-synuclein expression in neurons and other brain cells. Using a lipidomics approach we are investigating changes in global lipid profiles associated with Lewy body formation in human brain samples from Parkinson's disease compared to control subjects. This project is in collaboration with Prof Glenda Halliday, Neuroscience Research Australia.

Future Topics for Students

PhD student projects are available in association with the major research projects listed above.

Abbreviated CV

Professor Brett Garner leads the Cellular Lipidology Group at IHMRI. He obtained his PhD from Sydney University Faculty of Medicine in 1996 and has extensive postdoctoral research experience in cellular lipidology; including as a Wellcome Research Fellow in the Department of Biochemistry at Oxford University. His research focus is on the transport, metabolism and function of lipids including cholesterol and glycosphingolipids (GSLs) with an emphasis on understanding how lipid homeostasis contributes to neuronal function and degeneration; particularly in Alzheimer's disease and Parkinson's disease. This research is predominantly at a molecular and cellular level and is supplemented by studies of human brain tissue. Since an overriding goal is to develop novel neuroprotective pharmacological strategies, animal studies are also conducted that focus on control of lipid homeostasis in the central nervous system and the inhibition of amyloid-beta deposition in the brain.

Academic Qualifications

1989, BSc, Deakin University

1991, BSc (Hons I), University of Wollongong

1996, PhD, University of Sydney

Current Research Positions

Principal Research Fellow, Illawarra Health and Medical Research Institute, University of Wollongong

Professor, School of Biological Sciences, Faculty of Science, University of Wollongong

ARC Future Fellow, Illawarra Health and Medical Research Institute, University of Wollongong

NHMRC Senior Research Fellow (Honorary), Illawarra Health and Medical Research Institute, University of Wollongong

Principal Research Fellow (Honorary), Neuroscience Research Australia, Sydney, Australia

Current Editorial Positions with International Journals

J Alzheimer’s Dis, J Lipid Res, Clin Sci, Clin Lipidol, Biochem J

Previous Research Positions

2008 – 2009, Associate Professor, UNSW, Faculty of Medicine, Sydney, Australia

2002 – 2008, Senior Lecturer, UNSW, Faculty of Medicine, Sydney, Australia

2002 – 2004, NHMRC Florey Research Fellow, Centre for Vascular Research, UNSW, Faculty of Medicine, Sydney, Australia

2005 – 2009, NHMRC RD Wright Research Fellow, Prince of Wales Medical Research Institute, Sydney

2000 – 2002, Wellcome Trust Research Fellow, Dept of Biochemistry, University of Oxford, Oxford, UK

1997 – 1999, Research Officer, University of Wollongong, Faculty of Science

1995 – 1996, Research Officer, University of Sydney, Faculty of Medicine

1992 – 1995, PhD Research Scholar (APA Scholar), University of Sydney, Faculty of Medicine

Awards

1992, APA PhD Scholarship

1993, Australian Atherosclerosis Society Young Investigator Award

2002, Howard Florey Centenary Fellowship (NHMRC)

2003, Grace Arlene Bryant Award for Research Excellence (NHF)

2006, Peter Frilingos Memorial Award for Research Excellence (NHF)

Current Major Funding

2012 – 2014, NHMRC Project Grant (1024966) - Altered Myelin Sphingolipid Homeostasis in Alzheimer's Disease. Don A, Garner B, $608,375

2011 – 2013, NHMRC Project Grant (1003886) - Defining the Function of apolipoprotein-D in Alzheimer’s disease. Garner B, Karl T, $440,312

2011 – 2013, NHMRC Project Grant (1008307) - Cellular effects of glucocerebrosidase (GBA) mutations in Lewy body diseases. Halliday G, Sidransky E, Garner B, $506,706

2010 – 2013, ARC Future Fellowship (FT0991986) - Targeting brain lipid homeostasis to treat Alzheimer’s disease. Garner B $788,800

2010 – 2014, NHMRC Senior Research Fellowship (630445) - Targeting brain lipid homeostasis to treat Alzheimer’s disease. Garner B $672,000 (20% funding for 2014 only)

2012 - 2014, Anonymous Donation, Liquid Chromatography-Mass Spectrometry Infrastructure Support for Neurodegeneration Research. Garner B $427,690

2012, ARC LIEF Grant (LE120100045) - Integrated facility for confocal imaging and single molecule fluorescence analysis. Yerbury J, Wilson MR, Garner B, Dixon NE, Huang X-F, Olsson MM, Sunde M, Campbell IL, Truscott R. $300,000

Previous funding

2010 – 2011, NHMRC Project Grant (630452) - Neuregulin dependent neuronal migration and schizophrenia. Shannon-Weickert, C, Garner B, Fullerton J, $281,000

2009 – 2011, NHMRC Project Grant (568651) - Regulation of amyloid-beta production by sphingolipid synthesis inhibition. Garner B, Evin G, $486,600

2010, Anonymous Donation, Research Equipment Grant: Gas Chromatography-Mass Spectrometry Equipment for Brain Lipidomics Research. Garner B $197,950

2008 – 2010, NHMRC Project Grant (510148) - Role of ABCA/G transporters in neuronal cholesterol regulation and Alzheimer's disease. Garner B, Kim WS, Halliday GM, $554,246

2008 – 2010, NHMRC Project Grant (510217) - Biological characterisation of the familial neurodegeneration opioid receptor sigma 1 (OPRS1) gene. Kwok JBJ, Schofield PR, Garner B $477,202

2008, University of New South Wales Gold Star Research Grant – Garner B $40,000

2007, University of New South Wales Gold Star Research Grant - Garner B $40,000

2006, R. L. Cooper Medical Research Foundation, Research Grant - Garner B $20,000

2006, Clive and Vera Ramaciotti Foundation, Equipment Grant $25,000

2006 – 2008, NHMRC Project Grant (400909) - $528,000

2005 – 2009, NHMRC RD Wright Fellowship (350810) - $417,500

2005 – 2007, ARC, Discovery Project (DP0557295) - $325,000

2005 – 2006, National Heart Foundation, Grant in Aid (G04S1652) - $120,000

2005, Anonymous Donation, Research Equipment Grant: Inverted Research Microscope for Live Cell Imaging - $121,470

2004, ARC, LIEF Grant (LE0454209) - $295,000

2003 – 2004, National Heart Foundation, Grant in Aid (G02S0799) - $121,170

2003, R. L. Cooper Medical Research Foundation, Research Grant - $15,910