Facility Citations
  Associated Faculty
  Internal Users

home >> people >>
Michael E. Nesheim

  Protein Structure/Enzymology

  Contact Information:  
  Professor of Biochemistry & Medicine
B.Sc., Ph.D., Mayo Clinic Foundation, University of Minnesota;
International Society of Thrombosis and Hemostasis State-of-the-Art Lectureship Award

Tel: 613 533-2957
Fax: 613 533-2987
email: nesheimm@post.queensu.ca

  Our studies are directed toward obtaining an understanding of the properties of the components and reactions involved in the processes of blood coagulation and fibrinolysis. Ultimately we hope to understand the interactions by which these processes are regulated in vivo. The approach toward this involves studies of the structure and enzymology of the prothrombinase complex; studies of the heparin-catalyzed inhibition of coagulation Factors IIa and Xa by antithrombin III; and studies of the tissue-plasminogen-activator (tPA) induced lysis of fibrin clots. We also are investigating the plasma protein TAFI (Thrombin Activatable Fibrinolysis Inhibitor) and its enzyme TAFIa in order to more fully understand its role regulating the balance between fibrin formation and fibrin removal. All studies employ isolated and well characterized enzymes and other components, and utilize the classic techniques of protein chemistry and enzymology. In addition, modelling of the reactions of coagulation and fibrinolysis by computer simulation constitutes an integral component of our approach to understanding and describing these systems

  1. Boffa, M.B., Bell, R., Stevens, W.K. and Nesheim, M.E. Roles of Thermal Instability and Proteolytic Cleavage In Regulation of Activated TAFI. Journal of Biological Chemistry, In Press, 2000.

2. Nesheim,M.E. TAFI. Fibrinolysis & Proteolysis, 13(2):72-77, 1999.

3. Boffa,M.B., Reid,T.S., Joo,E., Nesheim, M.E., and Koschinsky, M.L. Characterization of the Gene Encoding Human TAFI (Thrombin-activable Fibrinolysis Inhibitor; Plasma Procarboxypeptidase B). Biochemistry, 38(20):6547-6558, 1999.

4. Walker, J.B., and Nesheim, M.E. The Molecular Weights, Mass Distribution, Chain Composition and Structure of Soluble Fibrin Degradation Products Released From a Fibrin Clot Perfused with Plasmin. Journal of Biological Chemistry, 274 (8):5201-5212, 1999.

5. Wang W., Boffa M.B., Bajzar L., Walker J., and Nesheim M.E. A Study of the Mechanism of Inhibition of Fibrinolysis by Activated Thrombin-activable Fibrinolysis Inhibitor. Journal of Biological Chemistry, 273(42): 27176-27181, 1998.

6. Boffa M.B., Wang W., Bajzar L., and Nesheim M.E. Plasma and Recombinant TAFI and TAFIa Compared With Respect To Glycosylation, Thrombin / Thrombomodulin-dependent Activation, Thermal Stability and Enzymatic Properties. Journal of Biological Chemistry, 273(4): 2127-2135, 1998.

7. Horrevoets A.J.G., Pannekoek H., and Nesheim M.E. A Steady-State Template Model That Describes the Kinetics of Fibrin-stimulated Glu1- and Lys78- Plasminogen Activation by Native Tissue-type Plasminogen Activator and Variants That Lack Either the Finger or Kringle-2 Domain. Journal of Biological Chemistry, 272:2183-2191, 1997.

8. Bajzar L., Morser J. and Nesheim M. E. TAFI, or Plasma Procarboxypeptidase B, Couples Coagulation and Fibrinolysis Through the Thrombin-Thrombomodulin Complex. Journal of Biological Chemistry, 271, 16603-16608, 1996.

9. Bajzar L., Manuel R., and Nesheim M. E. Purification and Characterization of TAFI, a Thrombin Activatable Fibrinolysis Inhibitor. Journal of Biological Chemistry, 270, 14477-14484, 1995.