John W. Weisel, Ph.D.

Description of Research Expertise

Research Interests
Intermolecular and cellular interactions in blood clotting, fibrinolysis, and atherosclerosis studied by molecular biophysical methods.

Key words: Intermolecular interactions, integrins, adhesive proteins, platelet aggregation, blood clotting, fibrinolysis, structural biology, transmission electron microscopy, scanning electron microscopy, computer image processing, viscoelasticity, fibrinogen, fibrin clot, plasminogen, osteopontin, plasminogen, atherosclerosis, hemostasis, thrombosis.

Description of Research
The research in this lab has focused on the molecular and cellular mechanisms of blood coagulation, fibrinolysis and atherosclerosis, as analyzed through the use of various biophysical and structural techniques, including visualization of molecules and supramolecular aggregates and measurements of mechanical properties of cellular and extracellular structures. We are investigating the function of various domains of fibrinogen using recombinant fibrinogens and dysfibrinogenemias, as well as conformational changes that occur. Structural studies designed to elucidate the intermolecular interactions in all steps of fibrin clot formation and fibrinolysis are being carried out. Relationships between clot structure and mechanical properties are also an important part of this work. Molecular mechanisms of the dissolution of the clot by the fibrinolytic system are under investigation. The interactions of integrins with various adhesive proteins and with the cytoskeleton is also a focus of research, especially in platelet aggregation and cellular and extracellular matrix interactions in atherosclerosis. The results of these studies have implications for basic mechanisms of protein-protein and protein-cell interactions as well as for clinical aspects of hemostasis, thrombosis and atherosclerosis.



Figure 1: Colorized scanning electron micrograph of a whole blood clot. Yuri Veklich and John Weisel.



Figure 2: Laser scanning confocal micrograph showing fibrinolysis of a platelet rich plasma blood clot. Reconstructed images at two different time points are shown in red and green to illustrate the changes that take place over time. Jean-Philippe Collet and John W. Weisel.

Rotation Projects for 2006-2007
1. Molecular mechanisms of platelet aggregation
2. Molecular mechanisms of fibrin assembly and fibrinolysis
3. Interactions of individual ligand-receptor pairs in vitro and on cells
4. Thrombus formation

Lab personnel:
Sekar Nagaswami, MD - Research Specialist
Rustem Litvinov, PhD - Senior Research Investigator
Irina Chernysh, PhD - Research Specialist
Jim Torbet, PhD - Visiting Scholar
Nolan Shenai - Undergraduate Student