Division of Hematology & Thromboembolism

Patricia Liaw

B.Sc., M. Sc., Ph.D.

Associate Professor, Division of Hematology and Thromboembolism, Department of Medicine

Member, Thrombosis and Atherosclerosis Research Institute (TaARI)

 

 

Biography

Dr. Liaw is an Associate Professor at McMaster University in the Department of Medicine in the Division of Hematology. She received her Ph.D. in 1998 at McMaster University in the Department of Medical Sciences (Hemostasis, Thromboembolism, and Atherosclerosis programme) under the supervision of Dr. Jeffrey Weitz. Dr. Liaw then spent two years as a postdoctoral fellow in the laboratory of Dr. Charles Esmon at the Cardiovascular Biology Research Program at the Howard Hughes Medical Institute at the Oklahoma Medical Research Foundation.

Dr. Liaw’s overall research interest is to study the mechanistic links between coagulation, inflammation, and apoptosis particularly those associated with (a) the pathophysiology of sepsis (ie. life-threatening infections) and (b) chemotherapy-induced thrombogenesis. Her approach is to integrate basic studies with clinical research projects to gain understanding into why vascular dysfunction occurs.

Her current research focuses on two key areas: (1) Basic and clinical research of activated protein C, the first effective biological therapy for the treatment of sepsis, and (2) basic and translational studies to elucidate why chemotherapeutic drugs induce a hypercoagulable state.

Dr. Liaw’s integrative research approach includes studies at the levels of cell biology, protein biochemistry, molecular biology, and clinical research studies. The techniques utilized in her research include flow cytometry, cytokine and apoptosis assays, surface plasmon resonance (BIACORE), fluorescence spectroscopy, enzyme kinetics, confocal microscopy, flow cytometry, tissue culture, protein expression and purification, functional studies of human plasma and blood leukocytes.

Selected Publications

Book Chapters:

  1. Liaw PC and Weitz JI. (2006) Coagulation Overview. In Albert RK, Slutsky A, Ranieri M, Takala J, Torres A (eds): Clinical Critical Care Medicine. Philadelphia , Elsevier.

Peer-Reviewed Journal Articles:

  1. Mukherjee S, Swystun LL, Mackman N, Wang J.G., Pond G, Beaudin S, Shin LYY, Levine MN, Liaw PC. (2011) Impact of chemotherapy on thrombin generation and on the protein C in patients with early stage breast cancer patients. Pathophysiology Haemost Thromb 37(2-4):88-97.
  2. Yazdan-Ashoori P, Liaw PC, Toltl L, Webb B, Kilmer G, Carter DE, Fraser DD. Elevated plasma matrix metalloproteinases and their tissue inhibitors in patients with severe sepsis. Crit Care Med March 23 [Epub ahead of print].
  3. Swystun LL, Mukherjee S, Levine M, Liaw PC. (2011) Cyclophosphamide and its metabolite acrolein upregulate thrombin generation and impair the protein C anticoagulant pathway in animal- and cell-based models. J Thromb Haemost. 2011 Apr;9(4):767-75.
  4. Ricciuto DR, dos Santos CC, Hawkes M, Toltl LJ, Conroy AL, Rajwans N, Lafferty EI, Cook DJ, Fox-Robichaud A, Kahnamoui K, Kain KC, Liaw PC, Liles C. (2011) Angiopoietin-1 and-2 are clinically informative prognostic biomarkers of morbidity and mortality in a longitudinal cohort of patients with severe sepsis. Crit Care Med.Apr;39(4):702-710.
  5. Toltl LJ, Austin RC, Liaw PC.(2011)Activated protein C protects against inflammation, apoptosis, and tissue factor procoagulant activity by regulating endoplasmic reticulum calcium depletion in blood monocytes. J Thromb HaemostMar;9(3):582-92.
  6. Hirayama S, Cypel M, Sato M, Anraku M, Liaw PC, Liu M, Waddell TK, Kashavjee S. (2009) Activated protein C in ischemia-reperfusion injury after experimental lung transplantation. J Heart and Lung TransplantationNov;28(11):1180-1184.
  7. Swystun, LL, Shin LYY, Beaudin S, Liaw PC. (2009) Chemotherapeutic agents doxorubicin and epirubicin induce a procoagulant phenotype on endothelial cells and blood monocytes. J Thromb Haemost Apr;7(4):619-26.
  8. Toltl LJ, Swystun LL, Pepler L, Liaw PC (2008) Protective effects of activated protein C in sepsis. Thromb Haemost Oct;100(4):582-92.
  9. Toltl LJ, Beaudin S, Liaw PC. (2008)Activated protein C upregulates interleukin-10 and inhibits tissue factor in blood monocytes.J Immunol181: 2165-2173.
  10. Toltl LJ, Shin LYY, Liaw PC. (2007) Activated protein C in sepsis and beyond: Update 2006. Frontiers in Bioscience 12:1963-72.
  11. Stephenson DA, Toltl L, Beaudin S, Liaw PC. (2006) Modulation of monocyte function by activated protein C. J Immunol 177(4):2115-22.
  12. Woodley-Cook J, Shin LYY, Caruso S, Beaudin S, Liaw PC. (2006) Effects of the chemotherapeutic agent doxorubicin on the protein C anticoagulant pathway. Molecular Cancer Therapeutics Dec;5(12):3303-11.
  13. Yano K, Liaw PC, Mullington JM, Shih S, Okada H, Bodyak N, Kang PM, Belikoff B, Buras J, Mizgerd JP, Toltl L, Karumanchi SA, Aird WC. (2006) VEGF is an important determinant of sepsis morbidity and mortality. J Experimental Med. June 12;203(6):1447-58.
  14. Liaw PC, Esmon CT, Kahnamoui K, Schmidt S, Kahnamoui S, Ferrell G, Beaudin S, Julian JA, Weitz JI, Crowther M, Loeb M, Cook DJ. (2004) Patients with severe sepsis vary markedly in their ability to generate activated protein C. Blood 104:3958- 3964.
  15. Liaw PC. (2004) Endogenous protein C activation in patients with severe sepsis. Crit Care Med. 32[Suppl.]:S214-S218.
  16. Liaw PC, Ferrell GL, Esmon CT. (2003) A monoclonal antibody against activated protein C allows rapid detection of activated protein C in plasma and reveals a calcium ion dependent epitope involved in Factor Va inactivation. J Thromb Haemost1(4):662-670.
  17. Liaw PC, Becker DL, Stafford AR , Fredenburgh JC, Weitz JI. (2001) Molecular basis for the susceptibility of fibrin-bound thrombin to inactivation by heparin cofactor II in the presence of dermatan sulfate, but not heparin. J. Biol. Chem.276:20959-20965.
  18. Liaw PC, Mather T, Oganesyan N, Ferrell GL, Esmon CT (2001). Identification of the protein C/Activated protein C binding sites on the endothelial cell protein C receptor: Implications for a novel mode of ligand recognition by an MHC class 1-type receptor. J. Biol. Chem. 276:8364-8370.
  19. Liaw PC, Neuenschwander PF, Smirnov M, Esmon CT. (2000) Mechanisms by which soluble endothelial cell protein C modulates protein C and activated protein C function. J. Biol. Chem. 275:5447-5452.
  20. Liaw PC, Austin RC, Fredenburgh JC, Stafford AR , Weitz JI. (1999) Comparison of heparin-and dermatan sulfate-mediated catalysis of thrombin inhibition by heparin cofactor II. J. Biol. Chem. 274:27597-27604.
  21. Liaw PC, Fredenburgh JC, Stafford AR , Tulinsky A, Austin RC, Weitz JI. (1998) Localization of the Thrombin-binding Domain on Prothrombin Fragment 2. J. Biol. Chem. 273:8932-8939.