Nancy R. Webb, Ph.D.
Room 535, Wethington Building
900 S. Limestone
University of Kentucky
Tel: (859)-323-4933 ext 81385
Listings on PubMed
• Department of Internal Medicine, Division of Endocrinology/Molecular Medicine
• Graduate Center for Nutritional Sciences
• B.A., Biology, University of Virginia
• Ph.D., Microbiology/Immunology, University of Kentucky
• NIH Predoctoral Fellow
• NIH Postdoctoral Fellow
• Atorvastatin Research Award
• Finalist, American Heart Association Irvine H. Page Young Investigator Research
Specific Interest in Nutrition:
Relationship between inflammation and cardiovascular disease produced by high fat, high cholesterol diets.
It has been recognized for many decades that one of the major risk factors for developing cardiovascular disease (atherosclerosis) is high levels of low density lipoproteins (LDL) in the blood. High density lipoproteins, however, are generally protective against cardiovascular disease risk. Research in Dr. Webb’s laboratory is focused on LDL and HDL metabolism, and how inflammation alters LDL and HDL structure and function. Of particular interest in Dr. Webb’s lab are secretary phospholipase A2 ( sPLA2) enzymes that are produced by cells in response to inflammatory stimuli. These enzymes hydrolyze phospholipids on the surface of HDL and LDL particles, which is hypothesized to lead to pathogenic effects in blood vessels. This hypothesis is tested in Dr. Webb’s lab using two approaches. For one approach, the effect of sPLA2 modifications of LDL and HDL is studied in vitro. For the second approach, genetically altered strains of mice are used to determine whether increased or decreased phospholipase activity in vivo leads to changes in the extent of high fat diet-induced cardiovascular disease. Results from these studies may identify novel targets for treating atherosclerosis in humans.
1. Webb, N.R., Connell, P.M., Graf, G.A., Smart, E.J., de Williers, W.J.S., de Beer, F.C., and van der Westhuyzen, D.R. (1998) SR-BII, an isoform of the scavenger receptor BI containing an alternate cytoplasmic tail, mediates lipid transfer between high density lipoprotein and cells. J. Biol. Chem. 273:15241-15248.
2. De Beer, F.C., Connell, P.M.,Yu, J., de Beer, M.C., Webb, N.R., and van der Westhuyzen, D.R. (2000) HDL modification by secretory phospholipase A2 promotes SR-BI interaction and accelerates HDL catabolism. J. Lipid Res. 41: 1849-1857.
3. Webb, N.R., Cai, L., Ziemba, K.S., Yu, J., Kindy, M.S., van der Westhuyzen, D.R., and de Beer, F.C. (2002) The fate of HDL particles in vivo after SR-BI mediated selective lipid uptake. J. Lipid Res. 43: 1890-1898.
4. Webb. N.R., Bostrom, M.A., Szilvassy, S.J., van der Westhuyzen, D.R., Daugherty, A., and de Beer, F.C. (2003). Macrophage-expressed Group IIA sPLA2 increases atherosclerotic lesion formation in LDL receptor-deficient mice. Arterioscler. Thromb. Vasc. Biol. 23: 263-268.
5. Eckhardt, E.R., Cai, L., Sun, B., Webb, N.R., and van der Westhuyzen, D.R. (2004) High density lipoprotein uptake by scavenger receptor SR-BII. J. Biol. Chem. 279: 14372-14381.
6. Wooton-Kee, C.R., Boyanovsky, B.B., Nasser, M.S., de Villiers, W.J.S., and Webb, N.R. (2004) Group V sPLA2 hydrolysis of LDL results in spontaneous particle aggregation and promotes macrophage foam cell formation. Arterioscler. Thromb. Vasc. Biol. 24: 762-767.
7. Webb, N.R. (2005) Secretory phospholipase A2 enzymes in atherogenesis. Curr Opin Lipidol. 16:341-4.
8. Boyanovsky, B.B., van der Westhuyzen, D.R., Webb, N.R. (2005) Group V sPLA2-modified LDL promotes foam cell formation by a SR-A and CD36 independent process that involves cellular proteoglycans. J. Biol. Chem. [Epub ahead of print Jul 21]