In addition to being involved in the control of blood loss upon damage to the vascular system, blood platelets have been implicated in the genesis of certain forms of cardiovascular disease, e.g., heart attack and stroke. Based on this consideration, a more complete understanding of the fundamental mechanisms involved in platelet activation and inhibition would facilitate the development of pharmacological agents useful in the prevention and/or management of thromboembolic diseases.
To this end, our research program employs a wide range of chemical, biochemical and pharmacological techniques to study blood platelet signal transduction pathways. Specifically, novel chemical and immunological tools are developed and in turn employed as pharmacological probes to: 1. elucidate the sequence of events leading to platelet activation; 2. identify and characterize specific proteins involved in the signal transduction process; and 3. investigate whether selective pharmacological intervention can regulate the state of human blood platelet reactivity.
Publications:
1. Knezevic, I., Dieter, J.P. and Le Breton, G.C.: Mechanism of IP3-induced aggregation in saponin-permeabilized platelets. J. Pharmacol. Exp. Therap. 260: 947-955, 1992.
2. Borg, C., Lam, S., Dieter, J., Lim, C., Komiotis, D., Venton, D. and Le Breton, G.C.: Anti-peptide antibodies against the platelet TXA2 receptor: production, purification and characterization. Biochem.Pharmacol. 45: 2071-2078, 1993.
3. Knezevic, I, Borg, C. and Le Breton, G.C.: Identification of Gq as one of the G-proteins which co-purify with human platelet TXA2/PGH2 receptors. J. Biol. Chem. 268: 26011-26018, 1993.
4. Borg, C., Lim C.T., Yeomans, D., Deiter, J.P., Komiotis, D., Anderson, E.G. and Le Breton, G.C.: Purification of TXA2/PGH2 receptors from rat brain, rabbit aorta and human platelets by immunoaffinity chromatography employing anti-peptide and anti-receptor antibodies. J. Biol. Chem. 269: 6109-6115, 1994.