Contacts

Brett Garner 2013

Professor Brett Garner

BSc, Deakin University, BSc (Hons I), UOW, PhD, University of Sydney

Email:     brettg@uow.edu.au
Phone:   +61 2 4298 1576
Fax:         +61 2 4221 8130
Office:    B32.306

 Research Interests

  • Apolipoprotein structure and function
  • ATP-binding cassette transporter function in the brain
  • Therapeutic targeting sphingolipid metabolism
  • Oxidative stress and lipid peroxidation
  • Neurodegeneration
  • Alzheimer’s disease

The Garner Group is located in the Illawarra Health and Medical Research Institute (IHMRI) in 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 function of apolipoproteins in the brain and how this contributes to neurodegeneration. A strong emphasis is placed on the identification of novel therapeutic targets that may lead to novel treatment for neurodegenerative diseases such as Alzheimer’s disease. An overview of current research projects is provided below.


Representative Publications

Selected peer-reviewed publications in chronological order. 

  1. 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.
  2. 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.
  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, 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.
  9. 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.
  10. Jessup W, Garner B, Dean RT (1998) Cell-mediated metal reduction and its role in LDL oxidation. In, Plasma Membrane Redox Systems and their Role in Biological Stress and Disease. Kluwer Academic Publishers. Dordrecht, The Netherlands. pp 267-277.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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. Exp Eye Res 71: 599-607.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. 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. 
  25. 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.
  26. 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.
  27. Garner B (2003) Apolipoprotein glycosylation and its potential influence in atherogenesis. Glycobiology 18: 865.
  28. 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. 
  29. 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.
  30. Tedla N, Glaros EN, Brunk UT, Jessup W, Garner B (2004) Heterogeneous expression of apolipoprotein-E by human macrophages. Immunology 113: 338-347.
  31. 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.
  32. 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.
  33. 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.
  34. 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.
  35. 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.
  36. 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.
  37. 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.
  38. 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.
  39. 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.
  40. 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.
  41. 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.
  42. 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.
  43. 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.
  44. 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.
  45. Cheng D, Kim WS, Garner B (2008) Regulation of alpha-synuclein expression by liver X receptor ligands in vitro. Neuroreport 19: 1685-1689.
  46. 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.
  47. 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.
  48. Garner B (2008) Myriocin as an atherosclerosis inhibitor. Future Lipidol 3: 221-224.
  49. 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.
  50. 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.
  51. 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.
  52. 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.
  53. 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.
  54. 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.
  55. 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 Alzheimer's Dis 16: 121-131.
  56. 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.
  57. 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.
  58. Elliott DA, Halliday GM, Garner B (2010) Apolipoprotein-E forms dimers in human frontal cortex and hippocampus. BMC Neurosci 11: 23.
  59. Elliott DA, Weickert CS, Garner B (2010) Apolipoproteins in the brain – implications for neurological and psychiatric disorders. Clin Lipidol 5: 555-573.
  60. Garner B (2010) Lipids and Alzheimer's disease. Biochim Biophys Acta 1801: 747-749.
  61. 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.
  62. 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.
  63. 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 Alzheimer's Dis 21: 193-205.
  64. 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.
  65. Piguet O, Garner B (2010) Vascular pharmacotherapy and dementia. Curr Vasc Pharmacol 8: 44-50.
  66. 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.
  67. 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.
  68. 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.
  69. 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.
  70. 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 Alzheimer's Dis 27: 441-452.
  71. Zhao H, Brunk UT, Garner B (2011) Age-related lysosomal dysfunction: an unrecognized roadblock for cobalamin trafficking? Cell Mol Life Sci 68: 3963-3969.
  72. 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.
  73. 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.
  74. 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.
  75. Sharpe LJ, Wong J, Garner B, Halliday GM, Brown AJ (2012) Is Seladin-1 really a selective Alzheimer’s disease indicator? J Alzheimer's Dis 30: 35-39.
  76. Wong J, Garner B (2012) Evidence that truncated TrkB isoform, TrkB-Shc can regulate phosphorylated TrkB protein levels. Biochem Biophys Res Commun 420: 331-335.
  77. 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 210: 363-374.
  78. Karl T, Cheng D, Garner B, Arnold JC (2012) The therapeutic potential of the endocannabinoid system for Alzheimer’s disease. Expert Opin Ther Targets 16: 407-420 .
  79. 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
  80. Wong J, Garner B, Halliday GM, Kwok JB (2012) Srp20 regulates TrkB pre-mRNA splicing to generate TrkB-Shc transcripts with implications for Alzheimer's disease. J Neurochem: 123: 159-171.
  81. Logge W, Cheng D, Chesworth R, Bhatia S, Garner B, Kim WS, Karl T (2012) Role of Abca7 in mouse behaviours relevant to neurodegenerative diseases. PLoS ONE: 7: e45959.
  82. Appelqvist H, Sandin L, Bjornstrom K, Sattig P, Garner B, Ollinger K, Kagedal K (2012) Sensitivity to lyosome-dependant cell death is directly regulated by lyosomal cholesterol content. PLoS ONE: 7: e50262 
  83. Abbott SK, Jenner AM, Mitchell TW, Brown SHJ, Halliday GM, Garner B (2013) An improved high-throughput lipid extraction method for the analysis of human brain lipids. Lipids 48:307-318.
  84. Garner B (2013) Assessment of ABCA7 function in Alzheimer’s disease models. J Neurochem 125 (Suppl 1):39-40.
  85. Cheng D, Logge W, Low JK, Garner B, Karl T (2013) Novel Behavioural Characteristics of the APPSwe/PS1ΔE9 Transgenic Mouse Model of Alzheimer's Disease. Behav Brain Res 245:120-127.
  86. Bhatia S, Jenner AM, Li H, Ruberu K, Spiro AS, Shepherd CE, Kril JJ, Kain N, Don A, Garner B (2013) Increased apolipoprotein-D dimer formation in Alzheimer's disease hippocampus is associated with lipid conjugated diene levels. J Alzheimer's Dis 35:475-486.
  87. Zhao P, Ruberu K, Li H, Garner B (2013) Analysis of subcellular [57Co]cobalamin distribution in SH-SY5Y neurons and brain tissue. J Neurosci Methods 217:67-74.
  88. Kim WS, Li H, Rubero K, Chan S, Elliott DA, Low JK, Cheng D, Karl T, Garner B (2013) Deletion of Abca7 increases cerebral amyloid-beta accumulation in the J20 mouse model of Alzheimer's disease. J Neurosci 33:4387-4394.
  89. Cheng D, Low JK, Logge W, Garner B, Karl T (2013) Novel behavioural characteristics of female APPSwe/PS1deltaE9 double transgenic mice. Behav Brain Res 260:111-118.
  90. Murphy KE, Gysbers, AM, Abbott SK, Tayebi N, Kim WS, Sidransky E, Cooper A, Garner B, Halliday GM (2014) Reduced glucocerebrosidase is associated with increased alpha-synuclein in sporadic Parkinson’s disease. Brain 137:834-848.
  91. Couttas TA, Kain N, Daniels B, Lim XY, Shepherd C, Kril J, Pickford R, Li H, Garner B, Don AS (2014) Loss of the neuroprotective factor Sphingosine 1-phosphate early in Alzheimer's disease pathogenesis. Acta Neuropathol Commun 2:9.
  92. Zhao H, Ruberu K, Li H, Garner B (2014) Perturbation of neuronal cobalamin transport by lysosomal enzyme inhibition. Biosci Rep 34, e00092.
  93. Cheng D, Low JK, Logge W, Garner B, Karl T (2014) Chronic cannabidiol treatment improves social and object recognition in double transgenic APPswe/PS1∆E9 mice. Psychopharmacology 231, 3009-3017.
  94. Abbott SK, Li H, Sanz Muñoz S, Knoch B, Batterham M, Murphy KE, Halliday GM, Garner B (2014) Altered ceramide acyl chain length and ceramide synthase gene expression in Parkinson’s disease. Mov Disord 29, 518-526.
  95. Cheng D, Spiro AS, Jenner AM, Garner B, Karl T (2014) Long-term cannabidiol treatment prevents the development of social recognition memory deficits in Alzheimer’s disease transgenic mice. J Alzheimer's Dis 42, 1383-1396.
  96. Zhao H, Li H, Ruberu K, Garner B (2015) Impaired lysosomal cobalamin transport in Alzheimer’s disease. J Alzheimer's Dis, 43:1017-1030.
  97. Murphy KE, Gysbers AM, Abbott SK, Spiro AS, Furuta A, Cooper A, Garner B, Kabuta T, Halliday GM (2015) LAMP2 protein isoforms are differentially affected in early Parkinson’s disease. Mov Disord, 30:1639-1647.
  98. Abbot SK, Jenner AM, Spiro, Batterham M, Halliday GM, Garner B (2015) Fatty acid composition of the anterior cingulate cortex indicates a high susceptibility to lipid peroxidation in Parkinson's disease. J Parkinsons Dis 5:175-185.
  99. Li H, Ruberu K, Sanz Muñoz S, Jenner AM, Spiro A, Zhao H, Rassart E, Sanchez D, Ganfornina M, Karl T, Garner B (2015) Apolipoprotein-D modulates amyloid pathology in APP/PS1 Alzheimer's disease mice. Neurobiol Aging, 36:1820-1833.
  100. Li H, Karl T, Garner B (2015) Understanding the function of ABCA7 in Alzheimer's disease. Biochem Soc Trans, 43:920-923.
  101. Kreilaus F, Spiro AS, Hannan AJ, Garner B, Jenner AM (2015) Brain cholesterol synthesis and metabolism is progressively disturbed in the R6/1 mouse model of Huntington's disease: A targeted GC-MS/MS sterol analysis. J Huntingtons Dis. 4:305-318.
  102. Kreilaus F, Spiro AS, McLean CA, Garner B, Jenner AM (2016) Evidence for altered cholesterol metabolism in Huntington's disease post mortem brain tissue. Neuropathol Appl Neurobiol. 42:535-46.
  103. Li H, Karl T, Garner B (2016) Abca7 deletion does not affect adult neurogenesis in the mouse. Biosci Rep. 36:e00308.
  104. Li H, Ruberu K, Katl T, Garner B (2016) Cerebral apolipoprotein-D is hypoglycosylated compared to peripheral tissues and is variably expressed in mouse and human brain regions. PLOS ONE: 11:e0148238.
  105. Couttas TA, Kain N, Suchowerska AK, Quek L-E, Turner N, Fath T, Garner B, Don AS. (2016) Loss of ceramide synthase 2 activity, necessary for myelin biosynthesis, precedes tau pathology in the cortical pathogenesis of Alzheimer’s disease. Neurobiol Aging. 43:89-100.
  106. Zhao H, Ruberu K, Li H, Garner B (2016) Cell type-specific modulation of cobalamin uptake by bovine serum. PLOS ONE: 11:e0167044.
  107. Kreilaus F, Spiro AS, Hannan AJ, Garner B, Jenner AM (2016) Therapeutic effects of anthocyanins and environmental enrichment in R6/1 Huntington’s disease mice. J Huntingtons Dis. 5:285-296.
  108. Sandin L, Bergkvist L, Nath S, Kielkopf C, Janefjord C, Helmfors L, Zetterberg H, Blennow K, Li H, Nilsberth C, Garner B, Brorsson A-C, Kågedal K (2016) Beneficial effects of increased lysozyme levels in Alzheimer’s disease modelled in Drosophila melanogaster. FEBS Journal. 283:3508-3522.
  109. Karl T, Garner B, Cheng D (2017) The therapeutic potential of the phytocannabinoid cannabidiol (CBD) for Alzheimer's disease. Behav Pharmacol. 28:142-160
  110. 110. Kim WS, Fu Y, Dobson-Stone C, Hsiao JT, Shang K, Hallupp M, Schofield PR, Garner B, Karl T, Kwok JBJ (2018) Effect of fluvoxamine on amyloid-beta peptide generation and memory. J Alzheimers Dis. 62:1777-1787.
  111. Kielkopf CS, Low JKK, Mok YF, Bhatia S, Palasovski T, Oakley AJ, Whitten AE, Garner B, Brown SHJ (2018) Identification of a novel tetrameric structure for human apolipoprotein-D. J Struct Biol. S1047-8477:30136-30139.
  112. Garner B, Ooi L (2018) Wnt is here! Could Wnt signalling be promoted to protect against Alzheimer's disease? J Neurochem. 144:356-359.
  113. Muñoz SS, Li H, Ruberu K, Chu Q, Saghatelian A, Ooi L, Garner B (2018) The serine protease HtrA1 contributes to the formation of an extracellular 25-kDa apolipoprotein E fragment that stimulates neuritogenesis. J Biol Chem. 293:4071-4084.

Searchable publications


Current Projects 

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 as well as the impact of specific ABCA7 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 ABCA7 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 familial Alzheimer's disease mutations with ABC transporter gene knock-out mice. This project is in collaboration with Dr Tim Karl, Western Sydney University. 

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 have also discovered that apoE 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 function. Our current objectives are to characterise the exact sequence apoE fragments and determine their potential neuroprotective functions in the brain. This project is in collaboration with other UOW researchers, Dr Lezanne Ooi and Ms Sonia Sanz-Muñoz.

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 other UOW researchers, Dr Simon Brown, Ms Claudia Kielkopf, and Dr Aaron Oakley, and with Dr Tim Karl, Western Sydney University.

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 Anthony Don, University of Sydney. 


Abbreviated CV

Professor Brett Garner obtained his PhD from Sydney University Faculty of Medicine in 1996 and has extensive postdoctoral research experience in biochemistry; including as a Wellcome Research Fellow in the Department of Biochemistry at Oxford University. His research focus is on the function of apolipoproteins in the brain and how such proteins contribute to neuronal function and degeneration; particularly in Alzheimer's disease. This research is predominantly at a molecular and cellular level and is supplemented by studies in human brain tissue and transgenic mice. . 

Academic Qualifications

1989,  BSc, Deakin University
1991,  BSc (Hons I), University of Wollongong
1996,  PhD, University of Sydney

Current Research Positions

NHMRC Senior Research Fellow, Illawarra Health and Medical Research Institute, University of Wollongong
Principal Research Fellow, Illawarra Health and Medical Research Institute, University of Wollongong
Professor, School of Biological Sciences, Faculty of Science, Medicine and Health, University of Wollongong

Editorial Positions with International Journals

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

Previous Research Positions

2010 – 2013, ARC Future Fellow, Illawarra Health and Medical Research Institute, University of Wollongong
2008 – 2009, Associate Professor, UNSW, Faculty of Medicine, Sydney, Australia
2005 – 2009, NHMRC RD Wright Research Fellow, Prince of Wales Medical Research Institute, Sydney
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
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

2018 – 2021, NHMRC Project Grant (1141789) – Cannabidiol (CBD): A novel therapeutic for Alzheimer's disease. Karl T, Ittner A, Garner B, $775,005
2016 – 2020, NHMRC Senior Research Fellowship (1109831) - Defining the mechanisms by which ABCA7 and apoE control Alzheimer's disease risk. Functional characterization of new therapeutic targets for dementia prevention and treatment. Garner B, $687,975
2016 – 2019, NHMRC Project Grant (1100626) – Restoring neuroprotective sphingosine 1-phosphate signalling in Alzheimer’s disease. Don A, Garner B, Fath T, Rosen H, $857,656

Previous funding

2015 – 2017, NHMRC Project Grant (1079995) – Isoform-dependent apoE processing by human induced pluripotent stem cells. A novel pathway linking APOE genotype and Alzheimer’s disease risk. Garner B, Ooi L, Li H, Sidhu K, $416,660
2014 – 2016, NHMRC Project Grant (1065982) – A novel roadblock to vitamin B12 transport in the brain. Garner B, $536,124
2015 - 2017, Anonymous Donation, Mass Spectrometry Support for Molecular Neurodegeneration Research. Garner B $363,210
2010 – 2015, NHMRC Senior Research Fellowship (630445) - Targeting brain lipid homeostasis to treat Alzheimer’s disease. Garner B $672,000
2012 - 2014, NHMRC Project Grant (1024966) - Altered Myelin Sphingolipid Homeostasis in Alzheimer's Disease. Don A, Garner B, $608,375 
2014, ARC LIEF Grant (LE140100118) – Regional flow cytometry facility. Wilson MR, Ecroyd H, Huang X-F, Sunde M, Olsson MM, Garner B, Dixon NE, $370,000
2012 - 2014, Anonymous Donation, Liquid Chromatography-Mass Spectrometry Infrastructure Support for Neurodegeneration Research. Garner B $427,690
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
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
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
2003,  Australian Atherosclerosis Society Trust, Travel Grant - $1000
2002 – 2004, NHMRC Howard Florey Centenary Fellowship (189990) - $164,287 
2002,  University of Linköping, Visiting Researcher Fellowship - $20,000
2000 – 2001, Wellcome Trust Fellowship (058833) - $201,290
1999,  University of Linköping, Visiting Researcher Fellowship - $10,000
1996,  National Heart Foundation, Travel Grant - $1,500
1996,  Society for Free Radical Research Australasia, Travel Grant - $1,000
1995,  University of Linköping, Visiting Researcher Fellowship - $30,000
1994,  Australian Atherosclerosis Society Trust, Travel Grant - $1000\
1992 – 1995, Australian Postgraduate Award - $51,000

Last reviewed: 26 July, 2018