dvrresearch

Dr David van Reyk


Dr David van Reyk Phone: +61 2 9514 2221 Fax: +61 2 9514 8206 David.vanReyk@uts.edu.au Academic Qualifications BAppSci (UTS), PhD (Sydney), GradCertHEd (UTS) Teaching Activities Dr van Reyk is a Senior Lecturer in the Department of Medical and Molecular Biosciences of the University of Technology, Sydney. He is principally involved in teaching human anatomy and physiology, and clinical chemistry to undergraduate students enrolled in the Faculties of Science and Nursing, Midwifery and Health. Research Interests and Activities Protein glycation in the Vascular Complications of Diabetes Mellitus and the Treatment of Diabetes-Associated Atherosclerosis People with diabetes have an increased likelihood (ca. 3-fold) of suffering from cardiovascular disease, and in Australia approximately 72% of these people die from coronary heart disease. This elevated risk occurs even with well-controlled blood glucose levels, and with people without elevated levels of blood cholesterol. While it is established that diabetes greatly increases the risk of the development and progression of atherosclerosis, the mechanism(s) by which this occurs has not been fully elucidated. Hyperglycaemia has been identified as an independent risk factor for the development of atherosclerosis. As a result, there has been substantial interest in the reactions of glucose with proteins relevant to atherosclerosis (i.e glycation and glycoxidation reactions). Aldehyde derivatives of glucose such as methylglyoxal and glycolaldehyde are formed through glucose autoxidation, amino acid and lipid oxidation, metabolism as well as during glycation. The plasma levels of these compounds are known to be increased in diabetes and it has been shown that these aldehydes glycate proteins at rates that are significantly greater than that for glucose. In a collaborative project with Prof Michael J Davies (Heart Research Institute: http://www.hri.org.au), we are looking at modifications to proteins brought on by reactions between proteins and reactive aldehydes (e.g. methylglyoxal, glyoxal and glycolaldehyde). We hypothesise that these modifications promote atherogenic processes such as macrophage foam cell formation. Research Topics for Honours and Postgraduate Students Aldehyde-mediated modifications to lipoproteins that promote atherosclerosis Cellular targets for the hypohalous acids and for aldehydes Prevention of the development and progression of diabetes-accelerated atherosclerosis using anti-glycation therapies Research Staff and Students Students jointly supervised with Prof Michael J Davies (Heart Research Institute): Mr Imran Rashid (PhD, 2004) Ms Fatemeh Moheimani (PhD, 2006) Ms Pam Sheahan (PhD, 2007) Other students supervised by David van Reyk Mr Fahd Ishmael (Honours 2008) The role of low-density lipoprotein modification by myeloperoxidase-derived oxidants in atherosclerosis (co-supervised with Dr Clare Hawkins, Heart Research Institute) Ms Luka McDonald (Honours 2008) Polymorphisms in the macrophage cation transporter SLC11A1 and their modulation of macrophage function (in collaboration with Drs Bronwyn O'Brien and Najah Nassif) Ms Tania Tsatralis (MSc 2007) Testosterones effect of the calcification of vascular smooth muscle cells in atherosclerosis (co-supervised with Dr Alison Heather, Heart Research Institute) Grants 2009 van Reyk D, Davies MJ, Brown BE Can histidine-containing dipeptides, like carnosine, block or reverse protein glycation in a mouse model of diabetes-associated atherosclerosis?, Eli Lilly, $37,000 2007 van Reyk D, Davies MJ Investigations of the anti-atherogenic properties of a histidine-containing dipeptide, carnosine, in a murine model of diabetes-accelerated atherosclerosis, Diabetes Australia Research Grant, $46,800 Publications (2004-2008) Book Chapters Rashid I, Brown BE, van Reyk DM, Davies MJ (2006) The roles of glycation and glycoxidation and advanced glycation end product formation in diabetes-induced atherosclerosis In: Cheema S K (ed.) Biochemistry of Atherosclerosis, Springer Verlag, New York, pp 247-283 Original publications in refereed journals Lloyd MM, van Reyk DM, Davies MJ, Hawkins CL (2008): HOSCN is a more potent inducer of apoptosis and protein thiol depletion in murine macrophage cells than HOCl or HOBr Biochemical Journal 414: 271-280 Rashid I, van Reyk DM and Davies MJ (2007) Carnosine and its constituents inhibit glycation of low-density lipoproteins that promotes foam cell formation in vitro. FEBS Letters 58, 1067-1070 Brown BE, Rashid I, van Reyk DM and Davies MJ (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. FEBS Journal 274: 1530-1541 Brown BE, Mahroof FM, Cook NL, van Reyk DM and Davies MJ (2006) Hydrazine compounds inhibit glycation of low-density lipoproteins and prevent the in vitro formation of model foam cells from glycoaldehyde-modified low-density lipoproteins. Diabetologia, 49: 775-783 van Reyk DM, Brown AJ, Mattsson Hult'en L, Dean RT, Jessup W (2006) Oxysterols in biological systems: sources, metabolism and pathophysiological relevance. Redox Report 11: 255-262 Mattsson Hult'en L, Ullstrom C, Krettek A, van Reyk D, Marklund SL, Dahlgren C, Wiklund, O (2005) Human macrophages limit oxidation products in low density lipoprotein. Lipids in Health and Disease, 4: 6