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Thrombosis Research Section Faculty
Full-Time Faculty (Primary Appointment)
Research Interests:
José A. López, M.D., Professor and Scientific Director,
Thrombosis Research Section, Departments of Medicine and Molecular
and Human Genetics, Baylor College of Medicine.
Work in our laboratory is focused on understanding the mechanisms
by which platelets interact with components of the vessel wall (subendothelium
and endothelium) and with leukocytes. Much of the work involves the
biology of the platelet glycoprotein (GP) Ib-IX-V complex, the receptor
that mediates the initial interactions of platelets with the blood
vessel wall. This multi-subunit receptor binds von Willebrand factor
to tether platelets from the rapidly flowing blood onto the subendothelium,
and recently we have demonstrated that it also plays important roles
in the interactions of platelets with intact endothelium, when the
endothelium has been activated to express surface P-selectin, and
with neutrophils and monocytes by binding the leukocyte integrin Mac-1
(aMb2). Thus,
the GP Ib-IX-V complex plays a number of vital roles in platelet biology
and work in the laboratory investigates several of these: defining
the binding sites within the complex for its ligands and counter-receptors,
examining the consequences of platelet interactions with endothelium
and leukocytes, signal transduction subsequent to receptor engagement,
genetic variations of the complex in human populations, and genetic
disorders.
Recent work in our laboratory has explored the roles of membrane
microdomains in hemostasis, beginning with their role in the functions
of the GP Ib-IX-V complex. This has led us to explore the possibility
that procoagulant microvesicles originating in platelets and leukocytes
may arise from these membrane microdomains. This work attempts to
integrate the hemostatic functions of platelets and the soluble coagulation
system. We have found that tissue-factor bearing microparticles found
in normal plasma are able to fuse with activated platelets, in the
process localizing almost all of the reactions of coagulation to one
surface—that of the active platelet.
Selected References:
1. Shrimpton, C.N., Borthakur, G., 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.
2. Dong, J.F., Moake, J.L., Nolasco, L., Bernardo, A., Arceneaux,
W., Shrimpton, C.N., Schade, A.J., McIntire, L.V., Fujikawa, K., and
López, J.A. ADAMTS-13 rapidly cleaves newly secreted ultra-large
von Willebrand factor multimers on the endothelial surface under flowing
conditions. Blood 2002;100(12):4033–9.
3. Schade, A.J., Arya, M., Gao, S. Diz-Küçükkaya,
R., Anvari, B., McIntire, L. V., López, J. A. and Dong, J.F.
Cytoplasmic truncation of GP Iba weakens
its interaction with von Willebrand factor and impairs cell adhesion.
Biochemistry 2003;42(7):2245–51.
4. Li, C.Q., Dong, J.F., and López, J.A. (2002) The mucin-like
macroglycopeptide region of glycoprotein Iba
to immobilized von Willebrand factor under flow. Thromb Haemost
2002;88(4):673–7.
5. Zhang, J., Bergeron, A.L., Yu, Q., Sun, C., McIntire, L.V., López,
J.A., Dong, J.F. Platelet aggregation and activation under complex
patterns of shear stress. Thromb Haemost 2002;88(5):817–21.
6. Arya,M., Anvari,B., Romo,G.M., Cruz,M.A., Dong,J-F., McIntire,L.V.,
Moake,J.L., and López, J.A. Ultra-large multimers of von Willebrand
factor form spontaneous high-strength bonds with the platelet GP Ib-IX
complex: Studies using optical tweezers. Blood 2002;99(11):3971-3977.
7. Baglia F.A., Shrimpton C.N., López, J.A., Walsh P.N. The
glycoprotein Ib-IX-V complex mediates localization of factor XI to
lipid rafts on the platelet membrane. J Biol Chem.2003;Jan
6 [epub ahead of print].
8. Arya, M., López, J. A., Romo, G.M., Cruz, M.A. Kasirer-Friede,
A., Shattil, S. J. and Anvari, B. Glycoprotein Ib-IX-mediated activation
of integrin aIIbb3:
Effects of receptor clustering and von Willebrand factor adhesion.
J. Thrombosis and Haemost., in press.
9. Malek, S.N., Larrucea, S., Dong, J.-F., and López, J.A.
Platelets of mice transgenic for an activated form of the tyrosine
kinase Syk exhibit increased sensitivity to collagen, in revision.
 ©1995-2003
Baylor College of Medicine
Email: medicine@bcm.tmc.edu
URL: http://public.bcm.tmc.edu/medicine/lopez.html
(Modified: June 5, 2003 )
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