Pharmacology

Paul K Jurasz

Dr Paul K Jurasz

Adjunct Associate Professor

Education:
BSc, Biological Sciences, University of Alberta, 1998
PhD, Pharmacology, University of Alberta, 2002

Teaching:

Research: Pharmacology of Platelet-derived Angiogenesis Regulators

Research Interests / Laboratory Techniques

Platelets are blood cells physiologically known for maintaining hemostasis and pathologically for forming thrombi that occlude arteries, which can result in heart attack and ischemic stroke. Although much is known about the molecular mechanisms that both stimulate and inhibit platelet function, little is known about platelet heterogeneity and whether biochemically distinct platelet subpopulations exist that regulate hemostasis/thrombobosis. Recently, we demonstrated a highly novel aspect of platelet biology, identifying platelet subpopulatons based on the presence or absence of an endothelial nitric oxide synthase (eNOS) signalling pathway with a differential ability to initiate and limit platelet function. Currently, we are investigating the pharmacological regulation of these platelet subpopulations in an attempt to develop more effective anti-platelet drugs to prevent heart attacks and stroke.

In addition, platelets play important roles in cancer metastasis and in the regulation of angiogenesis (new blood vessel growth). During hematogenous metastasis invading cancer cells then intravasate into the circulation where they must withstand the shear forces of flowing blood and evade immune cells. At this step they are aided by their interactions with platelets, with which they form tumor-platelet aggregates/emboli. This process, known as tumor cell-induced platelet aggregation (TCIPA), offers several advantages to metastatizing cancer cells. In my laboratory we study the pharmacological regulation of TCIPA and the reciprocal interactions between cancer cell subpopulations and platelets.

Finally, Platelets contain and generate abundant pro- and anti-angiogenic mediators such as vascular endothelial growth factor and angiostatin, which upon release from platelets granules help regulate new blood vessel growth. Consequently, we are exploring how these platelet-derived angiogenesis mediators influence endothelial cell growth, migration, and the ability to form capillaries in an attempt to inhibit growth of blood vessels to tumors and to promote therapeutic blood vessel growth for cardiovascular disease.

Selected Recent Publications

Radziwon-Balicka, A., Lesyk, G., Back, V., Fong, T., Loredo-Calderon, E.L., Dong, B., El-Sikhry, H., El-Sherbani, A.A., El-Kadi, A., Ogg, S., Siraki, A., Seubert, J.M., Santos-Martinez, M.J., Radomski, M.W., Velazquez-Martinez, C.A., Winship, I.R., Jurasz, P. Differential eNOS-signalling by platelet subpopulations regulates adhesion and aggregation. Cardiovascular Research. 113:1719-1731, 2017.

Govindasamy N, Yan M and Jurasz P. (2016) Incorporation of β-actin loading control into zymography. J Biol Methods 3(4). pii: e61. PMID: 28191477

Mojiri A, Stoletov K, Lorenzana Carrillo MA, Willetts L, Jain S, Godbout R, Jurasz P, Sergi CM, Eisenstat DD, Lewis JD and Jahroudi N. (2016) Functional assessment of von Willebrand factor expression by cancer cells of non-endothelial origin. Oncotarget [Epub ahead of print] PMID: 28035064

Maayah ZH, Althurwi HN, Abdelhamid G, Lesyk G, Jurasz P and El-Kadi AO. (2016) CYP1B1 inhibition attenuates doxorubicin-induced cardiotoxicity through a mid-chain HETEs-dependent mechanism. Pharmacol Res 105:28-43. PMID: 26772815

Yan M and Jurasz P. (2016) The role of platelets in the tumor microenvironment: From solid tumors to leukemia. Biochim Biophys Acta 1863(3):392-400. PMID: 26193075

Khan SR, Baghdasarian A, Nagar PH, Fahlman R, Jurasz P, Michail K, Aljuhani N and Siraki AG. (2015) Proteomic profile of aminoglutethimide-induced apoptosis in HL-60 cells: Role of myeloperoxidase and arylamine free radicals. Chem Biol Interact 239:129-38. PMID: 26102013

Lesyk G, Fong T, Ruvolo PP and Jurasz P. (2015) The potential of enzastaurin to enhance platelet aggregation and growth factor secretion: implications for cancer cell survival. J Thromb Haemost 13(8):1514-20. PMID: 25990653

Goldthorpe H, Jiang JY, Taha M, Deng Y, Sinclair T, Ge CX, Jurasz P, Turksen K, Mei SH and Stewart DJ. (2015) Occlusive lung arterial lesions in endothelial-targeted, fas-induced apoptosis transgenic mice. Am J Respir Cell Mol Biol 53(5):712-718. PMID: 25879383

Samokhvalov V, Zlobine I, Jamieson KL, Jurasz P, Chen C, Lee KS, Hammock BD, Seubert JM. (2014) PPARδ signaling mediates the cytotoxicity of DHA in H9c2 cells. Toxicol Lett pii: S0378-4274(14)01372-1. PMID: 25300478

Yan M, Lesyk G, Radziwon-Balicka A and Jurasz P. (2014) Pharmacological regulation of platelet factors that influence tumor angiogenesis. Semin Oncol 41(3):370-7. PMID: 25023352

Mojiri A, Nakhaii-Nejad M, Phan WL, Kulak S, Radziwon-Balicka A, Jurasz P, Michelakis E, Jahroudi N. (2013) Hypoxia results in upregulation and de novo activation of von Willebrand factor expression in lung endothelial cells. Arterioscler Thromb Vasc Biol. 33(6):1329-38. PMID: 23580145

Radziwon-Balicka A, Moncada de la Rosa C, Zielnik B, Doroszko A, Jurasz P. (2013) Temporal and pharmacological characterization of angiostatin release and generation by human platelets: implications for endothelial cell migration. PLoS One. 8(3):e59281. PMID: 23555012

Moncada de la Rosa C, Radziwon-Balicka A, El-Sikhry H, Seubert J, Ruvolo PP, Radomski MW, Jurasz P. (2013) Pharmacologic protein kinase Cα inhibition uncouples human platelet-stimulated angiogenesis from collagen-induced aggregation. J Pharmacol Exp Ther. 345(1):15-24. PMID: 23386249

Radziwon-Balicka A, Ramer C, Moncada de la Rosa C, Zielnik-Drabik B, Jurasz P. (2013) Angiostatin inhibits endothelial MMP-2 and MMP-14 expression: a hypoxia specific mechanism of action. Vascul Pharmacol. 58(4):280-91. PMID: 23220260

Radziwon-Balicka A, Moncada del la Rosa C, Jurasz P. (2012) Platelet-associated angiogenesis regulating factors: A pharmacological perspective. Can J Physiol Pharmacol. 90(6):679-88. PMID: 22512504

Jain S, Tran S, El Gendy MA, Kashfi K, Jurasz P, Velázquez-Martínez CA. (2012) Nitric oxide release is not required to decrease the ulcerogenic profile of nonsteroidal anti-inflammatory drugs. J Med Chem. 55(2):688-96. PMID: 22148253

Jurasz P, Vurkova N, Kirshenbaum LA, Stewart DJ. (2011) VEGF Masks BNIP3-mediated Apoptosis of Hypoxic Endothelial Cells. Angiogenesis 14(2):199-207. PMID: 21318419

Jurasz P, Courtman D, Babaie S, Stewart DJ. (2010) Role of apoptosis in pulmonary hypertension: from experimental models to clinical trials. Pharmacol Ther. 126(1):1-8. PMID: 20117135

Jurasz P, Ng D, Granton JT, Courtman D, Stewart DJ. (2010) Elevated platelet angiostatin and circulating endothelial microparticles in idiopathic pulmonary hypertension. Thromb. Res. 125, 53-60. PMID: 19427678