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Thrombosis Research Section Faculty
Full-Time Faculty (Primary Appointment)
Research Interests:
Platelet adhesion to vascular subendothelium or to other intravascular
surfaces is the initial event in both normal hemostasis and arterial
thrombosis, so a complete understanding of platelet adhesion is critical
to control hemorrhage as well as prevent arterial thrombosis. The
von Willebrand protein (VWF) has assumed a critical role in platelet
adhesion as it permits stable platelet adhesion under the high flow
high shear conditions present in the arterial circulation. We are
interested to define the molecular basis of platelet adhesion, particularly
the mechanism by which VWF adheres to collagen coated surfaces, is
then activated and binds to the platelet GpIb receptor. Our lab is
also studying the structure and function of the platelet collagen
receptor GPIa/IIa (integrin a2b1).
This receptor is important in the firm adhesion and activation of
platelets involved in thrombus formation. While numerous studies have
studied the role of GPIa/IIa in the process of collagen-induced platelet
activation, very recently some attention has been given to the platelet-mediated
activation of GPIa/IIa. Intracellular signals induce changes in the
integrin extracellular domain, resulting in integrin activation, as
manifested by an increase in affinity of the integrin for its ligands
We are especially interested in the molecular mechanism by which this
receptor is activated in order to interact with collagen.
Selected Publications:
1. Jan Schulte am Esch II, Simon C. Robson, and Miguel A. Cruz.
Platelet aggregation by membrane-expressed A1 domains of von Willebrand
Factor is dependent on residues Asp 560 and Gly 561. Biochem Biophys
Res Commun 2003;302:877-881.
2. Gautam Borthakur, Miguel A. Cruz, Jing-fei Dong, Larry McIntire,
Feng Li, José A. López and Perumal Thiagarajan. Sulfatides
Inhibit Platelet Adhesion to the von Willebrand Factor A1 Domain under
Flowing Blood. Thromb Haemost (2003) in press.
3. Maneesh Arya, Jose A. Lopez, Gabriel M. Romo, Miguel A. Cruz, Ana
Kasirer-Friede, Sanford J. Shattil, and Bahman Anvari. Glycoprotein
Ib-IX-mediated Activation of Integrin aIIbb3: Effects of Receptor
Clustering and von Willeberand Factor Adhesion. Thromb Haemost
(2003) In press.
4. Jody L. Whitelock, Jing-fei Dong, and Miguel A. Cruz. ADAMTS-13
cleaves recombinant von Willebrand Factor A2 domain. J Biol Chem
2003 (Submitted in revised form).
5. Jing-fei Dong, Joel L. Moake, Aubrey Bernardo, Chalmette Ball,
Leticia Nolasco, Kazuo Fujikawa, José A. López, and
Miguel A. Cruz. ADAMTS-13 metalloprotease interacts and cleaves ultra-large
von Willebrand factor under static and flowing conditions. J Biol
Chem 2003 (Submitted in revised form).
6. Shrimpton, C. Borthakur G., Larrucea S., Cruz M.A., Dong J.-F.
and. López, J. A. Localization of the Adhesion Receptor Glycoprotein
Ib-IX-V Complex to Lipid Rafts is Required for Platelet Adhesion and
Activation. J Exp Med 2002;196(8):1057-1066.
7. Fukuda K, Bankston LA, Cruz MA, Diacovo TG, Liddington RC. Structural
basis of von Willebrand factor activation by the snake toxin botrocetin.
Structure 2002;(10):943-50.
8. Smith C, Estavillo D, Emsley J, Bankston LA, Liddington RC, Cruz
MA. Mapping the collagen-binding site in the I domain of the glycoprotein
Ia/IIa (integrin alpha(2)beta(1)). J Biol Chem 2000;275:4205-9.
9. Cruz MA, Diacovo TG, Emsley J, Liddington R, Handin RI. Mapping
the glycoprotein Ib-binding site in the von Willebrand factor A1 domain.
J Biol Chem 2000;275:19098-105.
 ©1995-2003
Baylor College of Medicine
Email: medicine@bcm.tmc.edu
URL: http://public.bcm.tmc.edu/medicine/cruz.html (Modified: June 3, 2003)
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