Education and Professional Standing
- PhD, Biochemistry, University of Toronto 1971
- BSc, Biochemistry, McMaster University 1967
Platelet Responses to Thrombin
Research on platelets aimed primarily at determining the contributions of human protease activated receptors 1 and 4 in directing the responses of human platelets to thrombin, and identifying signaling pathways employed by the two receptors following their activation. My group is also interested in identifying cross talk between the two protease activated receptors and other G-protein-coupled receptors on platelets. Our group has demonstrated that protease activated receptor 1 (PAR-1) and not GPIB, is the primary binding site on human platelets for thrombin. Further, that PAR-1 cleavage necessarily precedes platelet activation in response to thrombin and SFLLRN (e.g., Liu et al, Br J Haematol 88: 592-600, 1994; Liu et al, J Biol Chem 272: 1997-2004, 1997; Ofosu et al, Biochem J 336: 283-285, 1998). Our group was the first to demonstrate that both PAR-1 and PAR-4 are cleaved in response to all concentrations of alpha-thrombin.
Gene Therapy for Hemophilia
In collaboration with Dr. Gonzalo Hortelano, we are exploring the feasibility of using encapsulated myoblasts engineered to secrete human FIX and FVIII to deliver FIX and FVIII, respectively, in hemophilic mice. The feasibility of this approach for therapeutic FIX delivery has now been established (e.g., Hortelano et al, Blood 87: 5095-5103, 1996; Hortelano et al, Human Gene Therapy 10: 1281-1288, 1999; Hortelano et al, Hemophilia 7: 207-214, 2001). Several significant safety issues associated with the use of transformed mouse myoblasts to deliver human FIX have been identified.
Sharon Craven, Lori Dewar, Myron Kulczycky, Xian Jun Yang