My laboratory is devoted primarily to investigating platelet physiology, vascular biology and adhesion phenomena in sickle cell disease. We had produced monoclonal antibodies that can inhibit platelet aggregation and the adhesion of sickle red blood cells to the blood vessel wall in an animal model system. One of these antibodies has been developed into a drug (abcixinab) to prevent ischemic complications of percutaneous coronary infarctions and unstable angina. Among the ongoing projects are:

• Platelet membrane receptors, including integrins (GPIIb/IIIa, V 3, 2 1), GPIb/IX and the thrombin receptor. Studies utilize monoclonal antibodies, synthetic peptides and recombinant techniques.

• Molecular-biologic basic of Glanzmann thrombasthenia (deficiency of platelet GPIIb/IIIa).

• Evaluation of a 3 knockout mouse as a model of Glanzmann thrombasthenia and to assess the role of 3-containing integrin receptors (GPIIb/IIIa and V 3) in thrombosis and other disease processes (sickle cell disease, tumor angiogenesis, stroke, atherosclerosis, intimal hyperplasia after vascular injury).

• Platelet adhesion to fibrinogen and collagen and passivation of thrombogenic surfaces.

• Platelet receptor blocking agents as therapeutics.

• Refinement of a point-of-care automated platelet function assay developed in collaboration with the scientists at Accumetrics for assessing platelet function and monitoring GPIIb/IIIa antagonist therapy.

• Assessment of adhesion of sickle cells to postcapillary venular endothelium and to leukocytes adherent to postcapillary venules in mouse models of sickle cell disease, as well as assessment of human sickle cell-human leukocyte interactions.

• Assessment of the role of platelet CD40 ligand (CD154) in the inflammatory response associated with vascular disease.

• Mechanisms of platelet-leukocyte interactions.

Publications