Link to All Robert M. Berne Cardiovascular Research Faculty

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Klaus  Ley
Degree(s): M.D.
Graduate School:
Julius-Maximilians-Univ of Wurzburg, Germany
Primary Appointment: Professor of Biomedical Engineering
Research Interests:
Leukocyte and Monocyte Adhesion and Activation in Inflammation and Atherosclerosis

Email Address: kfl3f@virginia.edu

Biomedical Sciences Graduate Program(s) 

Research Description

Inflammatory cell recruitment requires the concerted action of at least four major sets of adhesion molecules: integrins, immunoglobulin-like molecules, selectins, and carbohydrate structures serving as selectin ligands. Selectin-mediated adhesion represents the first step in the cascade required for leukocyte recruitment. The three known selectins (E-, L- and P-selectin) have been shown to be involved in mediating leukocyte rolling, which is a transient adhesion event during early inflammation. My laboratory investigates the involvement of the selectins in initial leukocyte attachment and emigration in vivo, mainly by using the method of intravital microscopy. We use blocking monoclonal antibodies, cell lines transfected with selectin molecules and selectin-deficient mice made by gene targeting and homologous recombination. Inflammation is experimentally induced by tissue trauma and/or injection of the pro-inflammatory cytokine TNF-alpha. Atherosclerotic lesions develop and progress through recruitment of monocytes into the arterial wall. This process appears to also involve adhesion molecules. Preliminary data suggest that P-selectin, L-selectin, and the immunoglobulin-like molecule VCAM-1 may be involved in monocyte recruitment into atherosclerotic lesions. We use an isolated perfused mouse carotid artery to study adhesion of monocytes and monocyte-like cell lines with the aim of identifying the relevant molecular mechanisms. The mouse model is useful because gene-targeted mice lacking apolipoprotein E (apoE) are available which develop atherosclerotic lesions. The results of this research are expected to augment the basic understanding of the inflammatory process as well as the potential for developing anti- inflammatory and anti-atherogenic therapies for future clinical use in patients.

Selected Publications

  • Huo Y, Zhao L, Hyman MC, Shashkin P, Harry BL, Burcin T, Forlow SB, Stark MA, Smith DF, Clarke S, Srinivasan S, Hedrick CC, Pratico D, Witztum JL, Nadler JL, Funk CD, Ley K. Critical role of macrophage 12/15-lipoxygenase for atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2004 Oct 5;110(14):2024-31.
  • Smith ML, Olson TS, Ley K. CXCR2- and E-Selectin-induced Neutrophil Arrest during Inflammation In Vivo. J Exp Med. 2004 Oct 4;200(7):935-9.
  • Olson TS, Bamias G, Naganuma M, Rivera-Nieves J, Burcin TL, Ross W, Morris MA, Pizarro TT, Ernst PB, Cominelli F, Ley K. Expanded B cell population blocks regulatory T cells and exacerbates ileitis in a murine model of Crohn disease. J Clin Invest. 2004 Aug;114(3):389-98.
  • Ley K, Kansas GS. Selectins in T-cell recruitment to non-lymphoid tissues and sites of inflammation. Nat Rev Immunol. 2004 May;4(5):325-35.
  • PubMed Listings for this Faculty Member
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      Office Address: PO Box 801394, MR-5, 1013, 
      Office Phone: +1 434-243-9966, +1 434-924-1722
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