Specialized Center of Research Laboratories
Platelets, Shear Stress, and Arterial Thrombosis
Responsible Investigator: José A. López, M.D.
Other Investigators: Jing-fei Dong, M.D., Ph.D.; Michael Berndt, Ph.D.
The overall objective of this project is to define the precise sequences within GP Iba (the ligand-binding subunit of the GP Ib-IX-V complex) involved in its interaction with vWf and to investigate the mechanism by which shear stress induces this interaction.
Molecular Mechanism of Shear-Induced Platelet Activation
Responsible Investigator: Michael Kroll, M.D.
Other Investigators: Andrew I. Schafer, M.D.; Michael Berndt, Ph.D.
The overall objective of this project is to investigate the initial sensing of shear stress by platelets, a process that may "prime" the GP Ib-IX-V complex to bind vWf, and the proximal intracellular signals transmitted subsequent to that binding.
Genetic Variation Affecting the GPIb-IX/IIb-IIIa Axis
Responsible Investigator: Paul F. Bray, M.D.
Other Investigators: José A. López, M.D.; Jing-fei Dong, M.D., Ph.D.; Vinod Vijayan, Ph.D.; Perumal Thiagarajan, M.D.
The overall objective of this project is to explore the relationship between observed differences in post-occupancy signaling and genetic variation in the two major platelet adhesion receptors, the GP Ib-IX-V complex and integrin aIIbb3 (GP IIb-IIIa).
Endothelial Cells, vWF Cleavage, and Thrombotic Microangiopathies
Responsible Investigator: Joel C. Moake, M.D.
Other Investigators: Michael Berndt, Ph.D.; Larry McIntire, Ph.D.
The overall objective of this project is to:
- examine the requirements of a plasma metalloprotease for cleaving ultra-large (UL) forms of vWf.
- evaluate whether the UL multimers of vWf that are responsible for most cases of sporadic and chronic relapsing thrombotic thrombocytopenic purpura TTP are also the proximal causative agents of other forms of acquired TTP.
- evaluate the potential for using agents that block vWf binding to platelets as agents to treat refractory TTP.