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

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, Louise Eltringham-Smith, Antje Ask

Graduate Students:
Ahmed Al-Arnawoot

Post-doctoral fellows:
David Donkor

Selected Publications

  • Scott BM, Sheffield WP. Engineering the serpin α(1) -antitrypsin: A diversity of goals and techniques. Protein Sci. 2019 Nov 27. doi: 10.1002/pro.3794. [Epub ahead of print].
  • Eltringham-Smith LJ, Yu R, Qadri SM, Wang Y, Bhakta V, Pryzdial EL, Crosby JR, Ni H, Sheffield WP. Prothrombin, alone or in complex concentrates or plasma, reduces bleeding in a mouse model of blood exchange-induced coagulopathy. Sci Rep. 2019;9:13029.
  • Sheffield WP, Eltringham-Smith LJ, Bhakta V. A factor XIa-activatable hirudin-albumin fusion protein reduces thrombosis in mice without promoting blood loss. BMC Biotechnol. 2018;18:21.
  • Sheffield WP, Eltringham-Smith LJ, Bhakta V. Fusion to Human Serum Albumin Extends the Circulatory Half-Life and Duration of Antithrombotic Action of the Kunitz Protease Inhibitor Domain of Protease Nexin 2. Cell Physiol Biochem.2018;45:772-782.
  • Donkor DA, Bhakta V, Eltringham-Smith LJ, Stafford AR, Weitz JI, Sheffield WP.  Selection and characterization of a DNA aptamer inhibiting coagulation factor XIa. Sci Rep. 2017;7:2102.
  • Qadri SM, Donkor DA, Bhakta V, Eltringham-Smith LJ, Dwivedi DJ, Moore JC, Pepler L, Ivetic N, Nazi I, Fox-Robichaud AE, Liaw PC, Sheffield WP. Phosphatidylserine externalization and procoagulant activation of erythrocytes induced by Pseudomonas aeruginosa virulence factor pyocyanin. J Cell Mol Med. 2016;20:710-20.
  • Sheffield WP, Bhakta V, Jenkins C. Stability of coagulation protein activities in single units or pools of cryoprecipitate during storage at 20-24°C for up to 24 h. Vox Sang. 2016;110:12-9.
  • Sheffield WP, Eltringham-Smith LJ, Gataiance S, Bhakta V. A plasmin-activatable thrombin inhibitor reduces experimental thrombosis and assists experimental thrombolysis in murine models. J Thromb Thrombolysis. 2015;39:443-51.
  • Eltringham-Smith LJ, Lei X, Reheman A, Lambourne MD, Pryzdial EL, Ni H, Sheffield WP. The fibrinogen but not the Factor VIII content of transfused plasma determines its effectiveness at reducing bleeding in coagulopathic mice. Transfusion. 2015;55:1040-50.
  • Sheffield WP, Lambourne MD, Eltringham-Smith LJ, Bhakta V, Arnold DM, Crowther MA. γT -S195A thrombin reduces the anticoagulant effects of dabigatran in vitro and in vivo. J Thromb Haemost. 2014;12:1110-5.
  • Scott BM, Matochko WL, Gierczak RF, Bhakta V, Derda R, Sheffield WP. Phage display of the serpin alpha-1 proteinase inhibitor randomized at consecutive residues in the reactive centre loop and biopanned with or without thrombin. PLoS One. 2014;9:e84491.

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