Joel S. Bennett, MD, Medline search
Professor of Medicine

914 BRB II/III
421 Curie Blvd.
Philadelphia, PA 19104

215-662-4028
215-573-7039 fax

Research Program
Molecular Analysis of the Platelet Glycoprotein IIb-IIIa Complex

Program Summary
Platelet aggregation results in the formation of the platelet plugs required for normal hemostasis and responsible for pathologic arterial thrombi. Platelet aggregation requires platelet activation and the subsequent exposure of binding sites for adhesive proteins such as fibrinogen, von Willebrand factor, and fibronectin on the platelet membrane GPIIb-IIIa complex. The objective of this research effort is understand the basis for platelet aggregation by studying the structure and function of GPIIb-IIIa This topic is of therapeutic interest because direct interruption of platelet aggregation is a promising mechanism for treating arterial thrombosis. Structure-function relationships in GPIIb-IIIa heterodimer are being examined by studying the function of mutant GPIIb-IIIa molecules. These studies have been facilitated by the development of a lymphocyte expression system in which recombinant GPIIb-IIIa can be activated by agonists such as phorbol esters. To further understand the changes in GPIIb-IIIa that occur when platelets are activated, regions of GPIIb and GPIIIa involved in the formation of the GPIIb-IIIa complex are being determined. These studies are being guided by focusing on regions of each molecule that associate with the intracellular chaperones involved in protein folding. The conclusions of these studies will then be related to the ultrastructure of GPIIb-IIIa using electron microscopy.