Haemostasis LaboratoryThe Blood PlateletMembers of Staff
Post-doctoral Research Scientists
Ph.D students
B.Sc. (Hons). Student
Research Assistants
Research ActivitiesPlatelets are specialised adhesive blood cells that play a central role in the blood clotting process (haemostasis). Upon damage to vessel walls, platelets rapidly attach to the site of injury (adhesion) and spread over the vascular subendothelium. This is followed by platelet-platelet cohesion (aggregation) leading to the formation of a primary haemostatic plug and the arrest of bleeding. However, the same process of platelet adhesion and aggregation is also responsible for the formation of vaso-occlusive thrombi, primarily occurring in atherosclerotic blood vessels. This exaggerated adhesion response often results in life threatening heart attacks or strokes, which are the major causes of death in developed countries. Platelet adhesion at sites of blood vessel injury requires glycoprotein receptors present on the platelet surface (GPIb/V/IX and GPIIb/IIIa or integrin IIb3) and adhesive proteins found in the vascular subendothelium (von Willebrand factor and collagen). The physiological importance of these adhesive interactions is highlighted by the severe bleeding disorders experienced by individuals with congenital deficiencies of GPIb/V/IX, integrin IIb3, or vWf. Under conditions of high blood flow such as those that are present in the arterial circulation and in pathologically stenosed vessels, the von Willebrand factor-GPIb/V/IX interaction becomes absolutely critical to initiate haemostasis. Following platelet adhesion to von Willebrand factor, integrin IIb3 becomes activated and participates in hemostasis although the underlying mechanisms of integrin IIb3 activation are as yet poorly characterised. The research focus of our laboratory is to gain a better understanding into the mechanisms regulating platelet adhesion and function to allow the identification of new drugs to correct an abnormal haemostatic or thrombotic platelet response. Current Research Projects
Selected Recent Publications (1999-2000)Cranmer SL, Ulsemer P, Cooke BM, Salem HH, de la Salle C, Lanza F and Jackson SP. Glycoprotein Ib/IX-transfected cells roll on a von Willebrand factor matrix under flow. Importance of the GPIb-Actin Binding Protein Interaction in Maintaining Adhesion under High Shear. J. Biol. Chem. 274:6097-6106, 1999 Williamson D, Giuliano S and Jackson SP. Platelet adhesion receptors: Novel targets for antithrombotic drugs. Aust NZ J Med 29:452-461, 1999 Yuan Y, Kulkarni, S, Ulsemer P, Cranmer SL, Yap CL, Mistry N, Nesbitt, WS, Harper, IS, Williamson, D, Dopheide SM, de la Salle C, Lanza F and Jackson SP. The von Willebrand factor—glycoprotein Ib/V/IX interaction induces actin polymerisation and cytoskeletal reorganisation in rolling platelets and glycoprotein Ib/V/IX-transfected cells. J. Biol. Chem. 274:36241-36251, 1999 Kulkarni S, Dopheide SM, Yap CL, Ravanat C, Freund M, Mangin P, Heel KA, Street A, Harper IS, Lanza F and Jackson SP. A Revised Model of Platelet Aggregation. J. Clin. Inv. 105:783-791, 2000
- Ruggeri ZM. Old concepts and new developments in the study of platelet aggregation. J. Clin. Inv. 105:699-701,2000 - Hinde J. Sticking point: There may be more to blood clots than meets the eye. New Scientist p18, April 1, 2000 Schoenwaelder SM, Yuan Y and Jackson SP. Calpain regulation of integrin IIb3 (GP IIb/IIIa) signalling in human platelets. Platelets, 11:189-198, 2000 Ulsemer P, Lanza F, Baas MJ, Schzartz A, Ravanat C, Briquel ME, Cranmer S, Jackson SP, Cazenave C, de la Salle C. Role of the leucine-rich domain of platelet GPIb-alpha for efficient processing and importance of the macroglycopeptide for normal adhesive function. The Bernard-Soulier Nancy 1 mutation reproduced in CHO cells. Thromb. Haemost. 84:104-111, 2000 Dopheide SM, Yap CL and Jackson SP. Dynamic aspects of platelet adhesion under flow. Clinical and Experimental Pharmacology and Physiology (In press), 2000 Mistry N, Cranmer SL, Yuan Y, Dopheide SM, Guiliano S, Harper IS, Dunstan D, De la Salle C, Lanza F, Salem HH and Jackson SP. Cytoskeletal regulation of the platelet GPIb/IX-von Willebrand factor interaction. Blood (In press), 2000 Yap CL, Hughan SC, Cranmer SL, Rooney MM, Dopheide SM, Kulkarni S, Yuan Y and Jackson SP. Synergistic adhesive interactions and signalling mechanisms operating between platelet glycoprotein Ib/IX and integrin IIb3 . Studies in human platelets and transfected CHO cells. J. Biol. Chem. (In press), 2000 Jackson SP, Nayna Mistry and Yuan Y. Platelets and the injured vessel wall —"Rolling into Action" — Focus on Glycoprotein Ib/V/IX and the Platelet Cytoskeleton. Trends. Cardiovasc. Med. (In press), 2000 Tait AS, Cranmer SL, Jackson SP, Dawes IW and Chong BH. Phenotype changes resulting in high—affinity binding of vWf to recombinant GPIb-IX: Analysis of the platelet-type von Willebrand disease mutations. Blood (Under revision), 2000
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