University of Virginia, Charlottesville, VA
University of Kentucky, Lexington, KY
Research in the Webb laboratory focuses on mechanisms of cardiovascular disease, including atherosclerosis and abdominal aortic aneurysms. It has been recognized for decades that high levels of HDL in the blood reduce an individual's risk for heart attack and stroke, yet it is not well understood why HDL (the "good cholesterol") is cardioprotective. The Webb laboratory studies what regulates HDL levels in the blood, how HDL functions to reduce cardiovascular risk, and how inflammation, obesity, and diabetes alter the ability of HDL to function. Research projects integrate biochemical, cellular, and physiological analyses of HDLs obtained from transgenic mouse models as well as human subjects. Another area of research in the Webb laboratory focuses on a family of lipolytic enzymes, the secretory phospholipase A2’s (sPLA2), and their role in physiological and pathophysiological processes. The underlying hypothesis of the studies is that lipid products generated by sPLA2’s serve as bioactive mediators that have pleiotropic effects on fat, vascular, and immune cells.
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. 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.
3. 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. 280:32746-52.
4. Bostrom, M.A., Boyanovsky, B.B., Jordan, C.T., Wadsworth, M.P., Taatjes, D.J., de Beer, F.C., and Webb, N.R. (2007) Group V secretory phospholipase A2 promotes atherosclerosis: Evidence from genetically altered mice. Arterioscler. Thromb. Vasc. Biol. 27:600-6.
5. Li, X., Shridas, P., Forrest, K., Baily, W., and Webb, N.R. (2010) Group X secretory phospholipase A2 negatively regulates adipogenesis in murine models. FASEB J. 24:4313-24. PMCID: PMC2974424
6. Boyanovsky, B. B., Bailey, W., Dixon, L., Shridas, P., and Webb, N.R. (2012) Group V secretory phospholipase A2 enhances the progression of angiotensin II-induced abdominal aortic aneurysms but confers protection against angiotensin II-induced cardiac fibrosis in apoE-deficient mice. Am. J. Pathol. 181:1088-98. PMCID: PMC3432434
7. De Beer, M.C., Wroblewski, J.M., Noffsinger, V.P., Rateri, D.L., Howatt, D.A., Balakrishnan, A., Ji, A., Shridas, P., Thompson, J., van der Westhuyzen, D.R., Tannock, L.R., Daugherty, A., Webb, N.R, de Beer F.C. (2014) Deficiency of endogenous acute phase serum amyloid A does not impact atherosclerotic lesions in apoE-/- mice. Arterioscler. Thromb. Vasc. Biol. 34: 255-261. PMCID: PMC3951741