Department of Regenerative Medicine and Cell biology

Kelley Argraves

Kelley Argraves, Ph.D.
Associate Professor

Room 650, Basic Science Building
Office: (843) 792-3535
Lab Phone: (843) 792-1430


Email: argravek@musc.edu

Argraves Laboratory Website
Education:

B.S. Biology, Mount St. Mary's College, Emmitsburg, MD
Ph.D. Biochemistry & Molecular Biology, The George Washington University, Washington, DC
Postdoctoral Fellow with Dr. Yusuf Hannun in the Biochemistry Department, MUSC, Charleston, SC

Research Interests:

Targeting endothelial barrier dysfunction with HDL-S1P therapeutics

Thus far, attempts at therapeutic elevation of HDL have not proved useful in reducing cardiovascular disease (CVD) risk in humans, despite evidence from epidemiological studies indicating that high levels of HDL cholesterol (HDL-C) inversely associate with risk for CVD. Findings from the laboratory of Dr. Kelley Argraves indicate that compositional differences of sphingolipids carried by HDL are related to the occurrence of ischemic heart disease (IHD), and suggest that these differences may contribute to the putative protective role of HDL in IHD and other vascular disorders. Specifically researchers in the Argraves lab have found a highly significant inverse relationship between the level of sphingosine 1-phosphate (S1P) in the HDL-containing fraction of serum and the occurrence of IHD (1). These findings support the hypothesis that the atheroprotective activity of HDL is at least in part a function of S1P content, with higher levels being protective. This agrees with emerging evidence suggesting that many of the effects of HDL on cardiovascular function may be attributable to its S1P cargo. Research in the Argraves lab also highlights potential mechanisms by which HDL-S1P may mediate preservation of normal endothelial cell (EC) function as a key component of its atheroprotective effects. Brent Wilkerson, a graduate student in the Argraves lab, has demonstrated that the amount of S1P on HDL correlates with the magnitude of HDL-induced EC barrier. Alteration in EC barrier function is a critical factor underlying several CVD-related processes, including post ischemic edema, recruitment and migration of monocytes, and introduction of triglyceride-rich lipoprotein particles into the intima of blood vessels. Brent has also shown that HDL-S1P also significantly prolongs maintenance of EC barrier function as compared to the other major S1P carrier in blood, albumin. Furthermore, they have evidence that patients with increased endothelial permeability and edema resulting from cardiopulmonary bypass have a reduction in postoperative plasma levels of HDL, the principle carrier of S1P in blood (2). Moreover, they have found that relative to albumin-S1P, HDL-S1P significantly prolongs maintenance of the phosphorylated state of eNOS, which catalyzes production of nitric oxide, a modulator of vascular tone and EC barrier. Together, findings from the Argraves lab highlight the potential therapeutic utility of HDL-S1P or agents that augment HDL-S1P levels to combat EC barrier dysfunction and atherosclerosis.

Recent Publications:

  1. Wilkerson, B. A., G. D. Grass, S. B. Wing, W. S. Argraves and K. M. Argraves. "Sphingosine 1-Phosphate (S1p) Carrier-Dependent Regulation of Endothelial Barrier: High Density Lipoprotein (Hdl)-S1p Prolongs Endothelial Barrier Enhancement as Compared with Albumin-S1p Via Effects on Levels, Trafficking, and Signaling of S1p1." J Biol Chem 287, no. 53 (2012): 44645-53 [PMID: 23135269]
  2. Zyblewski, S. C., W. S. Argraves, E. M. Graham, E. H. Slate, A. M. Atz, S. M. Bradley, T. C. McQuinn, B. A. Wilkerson, S. B. Wing and K. M. Argraves. "Reduction in Postoperative High-Density Lipoprotein Cholesterol Levels in Children Undergoing the Fontan Operation." Pediatr Cardiol 33, no. 7 (2012): 1154-9 [PMID: 22411716]
  3. Argraves, K. M., A. A. Sethi, P. J. Gazzolo, B. A. Wilkerson, A. T. Remaley, A. Tybjaerg-Hansen, B. G. Nordestgaard, S. D. Yeatts, K. S. Nicholas, J. L. Barth and W. S. Argraves. "S1p, Dihydro-S1p and C24:1-Ceramide Levels in the Hdl-Containing Fraction of Serum Inversely Correlate with Occurrence of Ischemic Heart Disease." Lipids Health Dis 10, (2011): 70 [PMID: 21554699]
  4. Bohonowych, J. E., S. Peng, U. Gopal, M. W. Hance, S. B. Wing, K. M. Argraves, K. Lundgren and J. S. Isaacs. "Comparative Analysis of Novel and Conventional Hsp90 Inhibitors on Hif Activity and Angiogenic Potential in Clear Cell Renal Cell Carcinoma: Implications for Clinical Evaluation." BMC Cancer 11, (2011): 520 [PMID: 22172030]
  5. Argraves, K. M., B. A. Wilkerson and W. S. Argraves. "Sphingosine-1-Phosphate Signaling in Vasculogenesis and Angiogenesis." World J Biol Chem 1, no. 10 (2010): 291-7 [PMID: 21537462]
  6. Argraves, W. S., A. Tanaka, E. P. Smith, W. O. Twal, K. M. Argraves, D. Fan and C. C. Haudenschild. "Fibulin-1 and Fibrinogen in Human Atherosclerotic Lesions." Histochem Cell Biol 132, no. 5 (2009): 559-65 [PMID: 19693531]
  7. Argraves, K. M., P. J. Gazzolo, E. M. Groh, B. A. Wilkerson, B. S. Matsuura, W. O. Twal, S. M. Hammad and W. S. Argraves. "High Density Lipoprotein-Associated Sphingosine 1-Phosphate Promotes Endothelial Barrier Function." J Biol Chem 283, no. 36 (2008): 25074-81 [PMID: 18606817]
  8. Gentile, C., P. A. Fleming, V. Mironov, K. M. Argraves, W. S. Argraves and C. J. Drake. "Vegf-Mediated Fusion in the Generation of Uniluminal Vascular Spheroids." Dev Dyn 237, no. 10 (2008): 2918-25 [PMID: 18816835]
  9. Argraves, K. M. and W. S. Argraves. "Hdl Serves as a S1p Signaling Platform Mediating a Multitude of Cardiovascular Effects." J Lipid Res 48, no. 11 (2007): 2325-33 [PMID: 17698855]
  10. Argraves, K. M., B. A. Wilkerson, W. S. Argraves, P. A. Fleming, L. M. Obeid and C. J. Drake. "Sphingosine-1-Phosphate Signaling Promotes Critical Migratory Events in Vasculogenesis." J Biol Chem 279, no. 48 (2004): 50580-90 [PMID: 15377653]
  11. Taha, T. A., K. M. Argraves and L. M. Obeid. "Sphingosine-1-Phosphate Receptors: Receptor Specificity Versus Functional Redundancy." Biochim Biophys Acta 1682, no. 1-3 (2004): 48-55 [PMID: 15158755]
  12. Argraves, K. M., L. M. Obeid and Y. A. Hannun. "Sphingolipids in Vascular Biology." Adv Exp Med Biol 507, (2002): 439-44 [PMID: 12664623]

 

 

 

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