Abstract

This proposal is to establish a Specialized Center of Research in Hemostatic and Thrombotic Diseases in the Texas Medical Center, based at the Baylor College of Medicine, Houston. The proposal focuses on the process of arterial thrombosis, beginning with the initial step of platelet adhesion mediated by the platelet glycoprotein (GP) Ib-IX-V complex and subendothelial von Willebrand factor (vWF), and culminating in the formation of a fibrin cross-linked thrombus that may completely occlude a blood vessel and cause tissue infarction. In addition to examining basic mechanisms of thrombus formation, we will investigate two clinical disorders, one a consequence of thrombosis, the thrombotic microangiopathies, and one complicated by thrombosis, peripheral arterial disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
5P50HL065967-04
Application #
6741473
Study Section
Special Emphasis Panel (ZHL1-CSR-F (S1))
Program Officer
Ganguly, Pankaj
Project Start
2001-06-06
Project End
2006-01-31
Budget Start
2004-03-29
Budget End
2005-01-31
Support Year
4
Fiscal Year
2004
Total Cost
$1,434,821
Indirect Cost

  Institution

Name
Baylor College of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Turner, Nancy; Nolasco, Leticia; Moake, Joel (2012) Generation and breakdown of soluble ultralarge von Willebrand factor multimers. Semin Thromb Hemost 38:38-46
Chen, Junmei; Reheman, Adili; Gushiken, Francisca C et al. (2011) N-acetylcysteine reduces the size and activity of von Willebrand factor in human plasma and mice. J Clin Invest 121:593-603
Chen, Junmei; Fu, Xiaoyun; Wang, Yi et al. (2010) Oxidative modification of von Willebrand factor by neutrophil oxidants inhibits its cleavage by ADAMTS13. Blood 115:706-12
Munday, A D; Gaus, K; López, J A (2010) The platelet glycoprotein Ib-IX-V complex anchors lipid rafts to the membrane skeleton: implications for activation-dependent cytoskeletal translocation of signaling molecules. J Thromb Haemost 8:163-72
Nambi, Vijay; Kimball, Kay T; Bray, Paul F et al. (2009) Differences in responses of platelets to fluid shear stress in patients with peripheral artery disease (PAD) and coronary artery disease (CAD). Platelets 20:199-205
Shah, Mona D; Bergeron, Angela L; Dong, Jing-Fei et al. (2008) Flow cytometric measurement of microparticles: pitfalls and protocol modifications. Platelets 19:365-72
Yago, Tadayuki; Lou, Jizhong; Wu, Tao et al. (2008) Platelet glycoprotein Ibalpha forms catch bonds with human WT vWF but not with type 2B von Willebrand disease vWF. J Clin Invest 118:3195-207
Moake, Joel L (2007) Journey in reverse: TTP from bedside to blood bank to bench. J Clin Apher 22:37-49
Auton, Matthew; Cruz, Miguel A; Moake, Joel (2007) Conformational stability and domain unfolding of the Von Willebrand factor A domains. J Mol Biol 366:986-1000
Nguyen, Trung C; Liu, Anne; Liu, Li et al. (2007) Acquired ADAMTS-13 deficiency in pediatric patients with severe sepsis. Haematologica 92:121-4

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