Professor of Bioengineering
B.S. Massachusetts Institute of Technology
Ph.D. University of California, Irvine
Susan Bock's Lab Page
Susan Bock's PubMed Literature Search
Biological Chemistry Program
Protein Conformational Change & Targeting
The lab works in the area of protein structure, function and design. Current projects are focused on understanding and modifying (1) the anticoagulant, anti-inflammatory and transport properties of the endogenous plasma glycoprotein antithrombin III, and (2) the antigenic properties of influenza hemagglutinins.
The antithrombotic and anti-inflammatory actions of antithrombin III are mediated through its binding to pentasaccharide-bearing heparan sulfate proteoglycans on vascular surfaces. To more effectively control pathological thrombotic and inflammatory processes which are initiated and propagated on vascular and biomaterial surfaces, we have modified (1) ATIII mass transport properties to increase surface loading by a factor of 7, and (2) ATIII neutrophil elastase cleavage and inactivation sensitivity to increase functional half-life by a factor of 10. Recombinant "super beta" antithrombin is a more efficient antithrombotic than endogenous, plasma-derived ATIII, doubling the time to occlusion in a rabbit ferric chloride - induced arterial thrombosis model. Neuroprotective properties of super beta antithrombins are also being evaluated in an animal model in which supraphysiological doses of plasma-derived antithrombin are effective at blocking secondary injury after spinal cord trauma, but cannot be used therapeutically due to concerns about increasing bleeding risk.
Immune responses to influenza virus infections and flu vaccines are primarily directed against a limited number of sites on its surface hemagglutinin. A new project focuses on understanding features that make primary antigenic determinants antigenic, and on modifying them to obtain broadly cross-protective vaccines..
- Dela Cruz RG, Jairajpuri MA, Bock SC (2006) Disruption of a tight cluster surrounding tyrosine-131 in the native conformation of antithrombin III activates it for factor Xa inhibition. J Biol Chem 281:31668-31676
- Bock SC, Picard V, Zendehrouh P (2005) Human Antithrombin IIIs and Methods Related Thereto. U.S. Patent #6,878,813
- Bock SC (2005) Antithrombin III and Heparin Cofactor II. Chapter 13 in Hemostasis and Thrombosis, Basic Principles and Clinical Practice , 5th edition. R.W. Colman et al., eds. J.B. Lippincott, Philadelphia
- Schedin-Weiss S, Desai UR, Bock SC, Olson ST, Björk I (2004) Roles of N-terminal region residues Lys11, Arg13 and Arg24 of antithrombin in heparin recognition and in promotion and stabilization of the heparin-induced conformational change. Biochemistry 43:675-83
- Jairajpuri MA, Lu A, Desai U, Olson ST, Bjork I, Bock SC (2003) Antithrombin III phenylalanines 122 and 121 contribute to its high affinity for heparin and its conformational activation. J. Biol. Chem. 278:15941-50
- Schedin-Weiss S, Desai UR, Bock SC, Gettins PGW, Olson ST, Bjork I (2002) The Importance of Lysine 125 for Heparin Binding and Activation of Antithrombin. Biochemistry 15:4779-4788
- Chuang YJ, Richard Swanson R, Raja SM, Bock SC, Olson ST (2001) The Antithrombin P1 Residue Is Important for Target Proteinase Specificity but Not for Heparin Activation of the Serpin. Characterization of P1 Antithrombin Variants with Altered Proteinase Specificity but Normal Heparin Activation. Biochemistry 40:6670-6679