McMaster University

McMaster University

William P. Sheffield

, PhD

Professor
Pathology and Molecular Medicine

Division: Molecular Medicine

McMaster University
4N66 Health Sciences Centre
905-525-9140 ext. 22701
sheffiel@mcmaster.ca

Currently accepting Graduate Students
Currently accepting Post-Doctoral Fellows

William P. Sheffield

Faculty Biography

Education and Professional Standing

  • PhD Biochemistry, McGill University, 1989
  • BSc(Hons) Biochemistry, McGill University, 1983

Interests

Research Focus

Research in the Sheffield laboratory focuses on plasma and plasma proteins in four general ways: in work aimed at producing novel plasma proteins with either procoagulant or anticoagulant properties; in work involving transfusion of plasma or plasma replacement products in animal models of coagulopathy and bleeding; in efforts to extend the circulatory lifetime of recombinant plasma proteins; and in quality monitoring of plasma and plasma products. Ongoing projects include: 1) Structure/function studies of the serine protease inhibitor (serpin) family members alpha-1-proteinase inhibitor, antithrombin, heparin cofactor II, and alpha-2-antiplasmin; 2) Fate of mutant albumin molecules in vivo in rabbits and mice, and efficacy in animal models of hemorrhage or thrombosis; 3) Gene fusion approaches to altering the clearance or distribution of plasma proteins (e.g. factors VII); and 4) Quality and efficacy of therapeutic plasma in vitro and in vivo. A variety of biochemical and molecular biological approaches are used, including site-directed and PCR-based mutagenesis of cDNAs, expression of recombinant proteins in bacterial, yeast, or cultured mammalian cell systems, protein characterization using enzymatic, immunochemical and biochemical techniques, in vivo studies of recombinant or natural proteins or protein mixtures injected into rabbits and/or mice, and characterization of the ability of plasma to support in vitro clotting.

Academic Interests

My educational focus is on biochemical and molecular biological aspects of health sciences. I have experience of problem-based learning in both the general undergraduate and undergraduate medical settings, as well as lecture- and laboratory-based courses in molecular and vascular biology, and inquiry.


Team Members

Research Assistants:
Varsha Bhakta, Sharon Gataiance,
Louise Eltringham-Smith, Melissa Lambourne

Graduate Students:
Richard Gierczak, Leigh Ann Roddick, Benjamin Scott

Selected Publications

  • Sheffield WP, Eltringham-Smith LJ, Bhakta V, Gataiance S. Reduction of thrombus size in murine models of thrombosis following administration of recombinant α1-proteinase inhibitor mutant proteins. Thromb Haemost. 2012;107:972-84.
  • Sheffield WP, Bhakta V, Mastronardi C, Ramirez-Arcos S, Howe D, Jenkins C. Changes in coagulation factor activity and content of di(2-ethylhexyl) phthalate in frozen plasma units during refrigerated storage for up to five days after thawing. Transfusion. 2012;52:493-502.
  • McCurdy TR, Bhakta V, Eltringham-Smith LJ, Gataiance S, Fox-Robichaud AE, Sheffield WP.  In vivo clearance of alpha-1 Acid glycoprotein is influenced by the extent of its N-linked glycosylation and by its interaction with the vessel wall. J Biomed Biotechnol. 2012;2012:292730. 
  • Gierczak RF, Sutherland JS, Bhakta V, Toltl LJ, Liaw PC, Sheffield WP. Retention of thrombin inhibitory activity by recombinant serpins expressed as integral membrane proteins tethered to the surface of mammalian cells. J Thromb Haemost. 2011; 9:2424-5.
  • Sheffield WP, Eltringham-Smith LJ. Incorporation of albumin fusion proteins into fibrin clots in vitro and in vivo: comparison of different fusion motifs recognized by factor XIIIa. BMC Biotechnol. 2011 Dec 20;11:127.
  • Sheffield WP, Bhakta V, Jenkins C, Devine DV. Conversion to the buffy coat method and quality of frozen plasma derived from whole blood donations in Canada. Transfusion 2010;50:1043-1049.
  • Sheffield WP, Eltringham-Smith LJ, Gataiance S, Bhakta V. Addition of a sequence from a2-antiplasmin transforms human serum albumin into a blood clot component that speeds clot lysis. BMC Biotechnol. 2009; Mar 3;9:15.
  • Sheffield WP. Eltringham-Smith LJ, Bhakta V, Gataiance S. A long-lasting, plasmin-activatable thrombin inhibitor aids in vitro clot lysis and does not promote bleeding in vivo. Thrombosis and Haemostasis 2009; 101: 867-77.
  • Sutherland JS, Bhakta V, Sheffield WP. The appended tail region of heparin cofactor II and additional reactive centre loop mutations combine to increase the reactivity and specificity of alpha-1-proteinase inhibitor M358R for thrombin. Thrombosis and Haemostasis 2007; 98: 1014-1023.
  • Sutherland JS, Bhakta V, Filion M, Sheffield WP. The transferable tail: Fusion of the N-terminal acidic domain of heparin cofactor II to alpha-1-proteinase inhibitor M358R specifically increases the rate of thrombin inhibition. Biochemistry 2006; 45: 11444-52.

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