McMaster University

McMaster University

Frederick A. Ofosu

, PhD

Professor Emeritus
Pathology and Molecular Medicine

Division: Molecular Medicine

Faculty of Health Sciences
McMaster University

ofosuf@mcmaster.ca

Faculty Biography

Education and Professional Standing

  • PhD, Biochemistry, University of Toronto 1971
  • BSc, Biochemistry, McMaster University 1967

Interests

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.


Team Members

Lab Technician

YingQi Song

Research Assistants

Sharon Craven, Lori Dewar, Myron Kulczycky, Xian Jun Yang

Graduate Student

Aisha Headley

Post-doctoral Fellow

Ling Yin

Selected Publications

  • F.A. Ofosu. Protease activated receptors 1 and 4 govern the responses of human platelets to thrombin. Transfusion and Apheresis Science 28: 265-268, 2003.
  • C. Garcia-Martin, M.K.L. Chnah, A. VanDamme, K.E. Robinson, B. Vanzieleghem, J-M. Saint-Remy, D. Gollordo, F.A. Ofosu, T. Vanderdriesshe, and G. Hortelano. Therapeutic levels of human factor VIII in mice implanted with encapsulated cells: potential for gene therapy of hemophilia A. Journal of Gene Medicine 4: 215-223, 2002.
  • F.A. Ofosu. The blood platelet as a model for regulating blood coagulation on cells and its consequences. Biochemistry (Moscow) 67: 47-55, 2002.
  • G. Hortelano, L. Wang, N. Xu, and F.A. Ofosu. Sustained and therapeutic delivery of factor IX in nude hemophilia B. Mice by encapsulated C2C12 myoblasts: Concurrent tumorigenesis. Hemophilia 7: 207-214, 2001.
  • M.I. Furman, P. Nurden, M.C. Berndt, A.T. Nurden, S.E. Benoit, A.L. Frelinger, M.J. Rohrer, M.R. Barnard, F.A. Ofosu, A.D. Michaelson. The cleaved peptide of PAR-1 results in a redistribution of the platelet surface GPIB-IX-X complex to the surface-connected canalicular system. Thromb. Haemost. 84: 897-903, 2000.
  • F.A. Ofosu, K.A. Nyarko. Human platelet thrombin receptors: roles in platelet activation. Hematol/Oncol Clin North Am. 14:1185-1198, 2000.
  • L. Liu, J. Freedman, A. Hornstein, J.W. Fenton II, Y. Song and F.A. Ofosu. Binding of thrombin to the G-protein linked receptor, and not to glycoprotein Ib, precedes thrombin-mediated platelet activation. J. Biol. Chem. 272:1997-2004, 1997.
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