- (859) 323-4933 ext. 81397
- 541 C.T. Wethington Bldg, 900 S Limestone St, Lexington, KY 40536-0200
- Imflammation and Lipoprotein Metabolism Research Group
- Univ. of the Witwatersrand, Johannesburg B.Sc. (Hons) 1967 Biochemistry
- Univ. of Cape Town, Cape Town, South Africa Ph.D. 1974 Biochemistry
- State Univ. of New York, Downstate Medical Postdoctoral 1976-1978 Biochem/Cell Biology
Research in my laboratory is focused on lipoprotein receptors and how such receptors contribute to or protect against atherosclerosis. Oxidized and modified lipoproteins play a key role in the development of atherosclerosis and our laboratory is studying various scavenger receptors that mediate the metabolism of such lipoprotein particles. One such receptor, the scavenger receptor-BI (SR-BI), is also a newly described receptor for HDL. SR-BI mediates the selective delivery of HDL cholesterol ester to cells and is a candidate receptor for mediating "reverse cholesterol transport" from extrahepatic tissues to the liver. We have shown that SR-BI exists as alternatively-spliced variants and we are currently studying the significance and biological functions of these receptor isoforms. This includes an investigation of the regulation of expression of SR-BI isoforms in different tissues and the regulation by cholesterol and oxidized lipids. The effect of dietary cholesterol and high fat "Western Diet" on the expression of scavenger receptors is also being studied. A central hypothesis being examined is that modification of HDL during inflammation leads to alterations in the interaction between HDL and SR-BI. Inflammation, as occurs in the atherosclerotic lesion, includes a wide variety of metabolic changes including a major modulation of HDL structure. Such changes would have important implications for HDL metabolism and could affect HDL-mediated cholesterol delivery to the liver, as well as cholesterol flux between HDL and cells in localized atherosclerotic lesions and the accumulation of cholesterol in the artery wall.
1. Cai L, de Beer MC, de Beer FC, van der Westhuyzen DR. Serum amyloid A is a ligand for scavenger receptor class B type I and inhibits high density lipoprotein binding and selective lipid uptake. J. Biol. Chem. 2005; 280: 2954-61. PMID:15561721
2. van der Westhuyzen DR, Cai L, de Beer MC, de Beer FC. Serum amyloid A promotes cholesterol efflux mediated by scavenger receptor-BI. J. Biol. Chem. 2005; 280: 35890-95. PMID:16120612
3. Eckhardt E, Cai L, Shetty S, Zhao Z, Szanto A, Webb NR, van der Westhuyzen DR. HDL endocytosis by scavenger receptor SR-BII is clathrin-dependent and requires a carboxy-terminal dileucine motif. J Biol Chem. 2005.
4. Eckhardt ER, Cai L, Shetty S, Webb NR, van der Westhuyzen DR,. High density lipoprotein endocytosis by scavenger receptor SR-BII is clathrin-dependent and requires a carboxyl-terminal dileucine motif. J Biol Chem. 2006; 281: 4348-53. PMID:16368683
5. Shetty S, Eckhardt ER, Post SR, van der Westhuyzen DR. Phosphatidylinositol-3-kinase regulates scavenger receptor class B type I subcellular localization and selective lipid uptake in hepatocytes. Arterioscler Thromb Vasc Biol. 2006; 26: 2125-31.