BCM Department of Medicine

Thrombosis Research Section Faculty

Full-Time Faculty (Primary Appointment)

Section Chief

PAUL F. BRAY, M.D.

Research Interests:

Dr. Bray's laboratory studies the role of platelets in cardiovascular disease, and disorders of bleeding and excessive blood clotting. His major areas of investigation include: (1) The role of platelets in coronary artery thrombosis, wherein he identifies and functionally characterizes platelet risk factors and their impact on cardiovascular therapy. His laboratory was the first to discover that the PlA2 polymorphism of integrin b3 is a risk factor for acute myocardial infarction and stroke. He has also shown that this polymorphism affects the ability of aspirin to inhibit platelets and that it confers a prothrombotic phenotype to normal human platelets and stably transformed cell lines. (2) Studies on gender differences in platelet function and thrombosis. He is studying this phenomenon as it as relates to acute vascular thromboses, since women have worse outcomes than men in these clinical settings. He has found that platelet fibrinogen binding is affected by sex hormones and that human platelets express the androgen receptor and estrogen receptor b but not estrogen receptor a or the progesterone receptor. (3) Studies on the prothrombotic nature of the platelet Fc receptor (FcgRIIa), a signaling molecule containing an ITAM domain. Dr. Bray has shown that an Arg/His131 polymorphism of FcgRIIa affects the phenotype of normal human platelets, and is investigating the effects of this polymorphism on cell signaling and platelet function. (4) Clinical epidemiology studies of patients with arterial thrombotic syndromes (MI, stroke, PAD) focusing on platelet hyperreactivity. He studies how gender and genetic variations in platelet adhesive molecules affect both the clinical and platelet phenotypes. (5) Molecular genetics of the inherited bleeding disorder, Glanzmann thrombasthenia using state-of-the-art techniques to detect mutations in the integrin aIIb and b3 genes.

Selected References:

1. Weiss EJ, Bray PF, Tayback M, Schulman SP, Kickler TS, Becker LC, Weiss JL, Gerstenblith G, Goldschmidt-Clermont PJ. A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis. N Engl J Med 334:1090-1094, 1996.

2. Jin Y, Wilhide CC, Li S-X, Li L, Villa-Garcia M, Dang CV, Bray PF. Human integrin b3 gene expression: evidence for a megakaryocytic cell-specific cis-acting element Blood 92:2777-2790, 1998.

3. Faraday N, Rade JJ, Johns DC, Khetawat G, Noga SJ, Dipersio JF, Jin Y, Nicol JL, Haug JS, Bray PF. Ex vivo cultured human megakaryocytes contain a functional GPIIb-IIIa receptor and can express exogenous gene products. Blood 94:4084-4092, 1999.

4. Michelson AD, Furman MI, Goldschmidt-Clermont P, Mascelli MA, Hendrix C, Coleman L, Hamlington J, Barnard MR, Kickler T, Christie DJ, Kundu S, Bray PF. Platelet GPIIIa PlA polymorphisms display different sensitivity to agonists and antagonists. Circulation 101:1013, 2000.

5. Vijayan KV, Goldschmidt-Clermont PJ, Roos C, Bray PF. The PlA2 polymorphism of integrin b3 enhances outside-in signaling and adhesive functions. J Clin Invest 105:793-802, 2000.

6. Khetawat G, Faraday N, Nealen M, Bolton E, Noga S, Bray PF. Human megakaryocytes and platelets contain the estrogen receptor b and androgen receptor (AR): testosterone regulates AR expression. Blood 95:2289-2296, 2000.

7. Bray PF, Cannon CP, Goldschmidt-Clermont P, Moyé LA, Richardson C, Pham Y, Pfeffer MA, Sacks FM, Braunwald E. The platelet PlA2 and angiotensin-converting enzyme (ACE) D allele polymorphisms and the risk of recurrent events after acute myocardial infarction. Am J Card 88:347-52, 2001.

8. Nealen ML, Vijayan KV, Bolton ED, Bray PF. Human platelets contain a glycosylated estrogen receptor b (ER b). Circ Res 28: 438-442, 2001.

9. Woods D, Cherwinski H, Venetsanakos E, Bray PF, Saylor VL, McMahon M. Induction of b3-integrin by Ras and Raf links sustained activation of the ERK/MAP kinase pathway to alterations in cell adhesion. Mol Cell Biol 21:3192-3205, 2001.

10. Braunstein JB, Kershner DW, Bray P, Gerstenblith G, Schulman SP, Post WS, Blumenthal RS. Interaction of hemostatic genetics with hormone therapy: new insights to explain arterial thrombosis in postmenopausal women. Chest 121:906-920, 2002.

11. Sajid MA, Vijayan KV, Souza SN, Bray PF. The PlA polymorphism of integrin b3 differentially modulates cellular migration on extracellular matrix proteins. Arterioscler Thromb Vasc Biol 22:1984-1989, 2002.

12. Vijayan KV, Liu Y, Dong J-F, Bray PF. Enhanced activation of mitogen activated protein kinase and myosin light chain kinase by the Pro33 polymorphism of integrin b3. J Biol Chem 78:3860-386, 2003.

13. Chen J, Dong J-F, Sun C, Bergeron A, McBride L, Pillai M, Barnard MR, Salmon J, Michelson AD, Bray PF. Platelet FcgRIIA His131Arg polymorphism and platelet function: antibodies to platelet bound fibrinogen induce platelet activation. J Thromb Haemost 1:355-362, 2003.

14. Vijayan KV, Huang TC, Liu Y, Bernardo A, Dong J-F, Goldschmidt-Clermont P, Alevriadou BR, Bray PF. Shear stress auguments the enhanced adhesive phenotype of cells expressing the Pro33 isoform of integrin b3. FEBS Letters 540:41-6, 2003.

Email: medicine@bcm.tmc.edu
URL: http://public.bcm.tmc.edu/medicine/bray.htm (Modified:June 3, 2003)