Hematology In the Department of Medicine

The Laboratory of Lawrence Lit King Leung, MD

Our lab interests include:

  1. Identification of Novel Endothelial Cell Genes
    We are using SAGE and microarray transcript profiling technologies to characterize genes that are expressed in specific vascular beds and during endothelial cell activation. We will study their expression and regulation in normal vascular biology and in various thrombotic and inflammatory vascular diseases.

    thumbnail of microarray
    Click for a larger represenation of the Microarray

  2. Biology and Biochemistry of Thrombin
    We are using a large collection of thrombin mutants generated by alanine scanning mutagenesis to study thrombin's diverse macromolecular substrate interactions. The long-term goal is to understand the regulation of thrombin's prothrombotic and proinflammatory activities with the potential of developing novel antithrombotic agents.

    Various Images

Timothy Myles, PhD

Yung-Jen Chuang, PhD

Shadi Sharif, BS, Lab Manager

Representative Publications

  1. Tsiang M, Jain AK, Dunn KE, Rojas ME, Leung LLK, Gibbs CS. Functional mapping of the surface residues of human thrombin. J. Biol. Chem. 270:16854-16863, 1995
  2. Tsiang M, Gibbs CS, Griffin LC, Dunn KE, Leung LLK. Selection of a suppressor mutation that restores affinity of an oligonucleotide inhibitor for thrombin using in vitro genetics. J. Biol. Chem. 270:19370-19376, 1995.
  3. Gibbs CS, Coutre SE, Tsiang M, Li WX, Jain AK, Dunn KE, Law VS, Mao CT, Matsumura SY, Mejza SJ, Paborsky LR, Leung LLK. Conversion of thrombin into an anticoagulant by protein engineering. Nature 378:413-416, 1995
  4. Tsiang M, Paborsky LR, Li W-X, Jain AK, Mao CT, Dunn KE, Lee DW, Matsumura SY, Matteucci MD, Coutre SE, Leung LLK, Gibbs CS. Protein engineering thrombin for optimal specificity and potency of anticoagulant activity in vivo. Biochemistry, 35:16449-16457, 1996
  5. Hall SW, Gibbs CS, Leung LLK. Strategies for development of novel antithrombotics: modulating thrombin's procoagulant and anticoagulant properties (mini-review). Cell. Mol. Life Sci. 53:731-736, 1997
  6. Hall SW, Nagashima M, Zhao L, Morser J, and Leung LLK. Thrombin interacts with thrombomuodulin, protein C, and thrombin-activatable finbrinolosysi inhibitor via specific and distinct domains. J. Biol. Chem., 1999, 274:25510-25516.
  7. Ramakrishnan V, DeGuzman F, Bao M, Hall SW, Leung LLK, and Phillips DR. A novel thrombin receptor function for platelet GPIb-IX unmasked by cleavage of GPV. Proc. Natl. Acad. Sci. USA, 2001, 98:1823-1828.
  8. Myles T, Yun TH, Hall SW, Leung LLK. An extensive interaction interface between thrombin and factor V is required for factor V activation. J. Biol. Chem. , 2001, 276:25143-25149.
  9. Hall SW, Gibbs CS, and Leung LLK. Identification of critical residues on thrombin mediating its interaction with fibrin. Thrombosis and Haemostasis 2001, 86:1466-1474.
  10. Myles T, Yun TH, Hall SW, Leung LLK.The structural requirements for the activation of human factor VIII by thrombin. Blood, 2002, 100:2820-2826.
  11. Philippou H, Rance J, Myles T, Hall SW, Ariens RA, Grant PJ, Leung L, Lane D. Roles of low specificity and cofactor interaction sites in factor XIII activation: competition for cofactor sites on thrombin determines its fate. J. Biol. Chem., 2003, 278:32020-32026.
  12. Yun TH, Baglia FA, Myles T, Navaneetham D, López JA, Walsh PN, Leung LLK. Thrombin activation of factor XI on activated platelets requires the interaction of factor XI and platelet glycoprotein Ib a with thrombin anion binding exosites I and II respectively. J. Biol. Chem., 2003, 278:48112-48119.
  13. Myles T, Yun TH, Nishimura T, Leung LLK. Thrombin activatable fibrinolysis inhibitor (TAFI): A potential regulator of inflammation. J. Biol. Chem., 2003, 278:51059-51067.
  14. Zhang WQ, Chuang YJ, Swanson R, Li J, Seo K, Leung L, Lau L and Olson ST. Antiangiogenic antithrombin down-regulates the expression of the pro-angiogenic heparin sulfate proteoglycan, perlecan, in endothelial cells. Blood, 2004, 103:1185-1191.

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