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John
W. Weisel
Professor, Dept of Cell and Developmental Biology
Cell
Biology and Physiology Program
Address
1054 Biomedical Rsch Bldg (BRB) II/III
421 Curie Boulevard
Philadelphia, PA 19104-6058
Office tel.: 215 898-3573
Lab tel.: 215 898-9141
Fax: 215 898-9871
E-mail: weisel@cellbio.med.upenn.edu
Link(s)
Dr.
Weisel's Cell & Developmental Biology Page
EDUCATION
Swarthmore College: BS (Electrical Engineering), 1968.
Brandeis University: PhD (Biophysics), 1974.
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RESEARCH
INTERESTS
- Intermolecular and cellular interactions in blood clotting,
fibrinolysis, and atherosclerosis studied by molecular biophysical
methods.
Key
words: Intermolecular interactions,
integrins, adhesive proteins, platelet aggregation, blood
clotting, fibrinolysis, structural biology, transmission electron
microscopy, scanning electron microscopy, computer image processing,
viscoelasticity, fibrinogen, fibrin clot, plasminogen, osteopontin,
plasminogen, atherosclerosis, hemostasis, thrombosis.
Search PubMed for articles
DESCRIPTION
OF RESEARCH
The research in this lab has focused on the molecular and
cellular mechanisms of blood coagulation, fibrinolysis and
atherosclerosis, as analyzed through the use of various biophysical
and structural techniques, including visualization of molecules
and supramolecular aggregates and measurements of mechanical
properties of cellular and extracellular structures. We are
investigating the function of various domains of fibrinogen
using recombinant fibrinogens and dysfibrinogenemias, as well
as conformational changes that occur. Structural studies designed
to elucidate the intermolecular interactions in all steps
of fibrin clot formation and fibrinolysis are being carried
out. Relationships between clot structure and mechanical properties
are also an important part of this work. Molecular mechanisms
of the dissolution of the clot by the fibrinolytic system
are under investigation. The interactions of integrins with
various adhesive proteins and with the cytoskeleton is also
a focus of research, especially in platelet aggregation and
cellular and extracellular matrix interactions in atherosclerosis.
The results of these studies have implications for basic mechanisms
of protein-protein and protein-cell interactions as well as
for clinical aspects of hemostasis, thrombosis and atherosclerosis.
RECENT
PUBLICATIONS
Weisel, J.W., Shuman, H., and Litvinov, R.I.: "Protein-protein
unbinding induced by force: Single-molecule studies,"
Current Opinion in Struct. Biol. 13:227-235,
2003.
Lim, B.C.B., Ariëns, R. A. S., Carter, A.M., Weisel,
J. W., and Grant, P. J.: "Genetic regulation of fibrin
structure and function: complex gene-environment interactions
may modulate vascular risk," Lancet 361:1424-1431,
2003.
Li, R., Mitra, N., Gratkowski, H., Vilaire, G., Litvinov,
R., Nagaswami, C., Weisel, J.W., Lear, J.D., DeGrado, W.F.,
and Bennett, J.S.: "Activation of integrin alphaIIbbeta3
by modulation of transmembrane helix associations," Science
300:795-798, 2003.
Collet, J.-P., Lesty, C., Montalescot, G., and Weisel, J.W.:
"Dynamic Changes of Fibrin Architecture during Fibrin
Formation and Intrinsic Fibrinolysis of Fibrin-rich Clots,"
J. Biol. Chem. 278: 21331-21335,
2003.
Standeven, K.F., Grant, P.J., Carter, A.M., Scheiner, T.,
Weisel, J.W., and Ariëns, R.A.S.: "Functional Analysis
of the Fibrinogen Aalpha Thr312Ala Polymorphism: Effects on
Fibrin Structure and Function" Circulation 107:2326-2330,
2003.
Lab
ROTATION
PROJECTS FOR 2006-2007
- Molecular mechanisms of platelet aggregation
- Molecular mechanisms of fibrin assembly and fibrinolysis
- Interactions of individual ligand-receptor pairs in vitro
and on cells
- Thrombus formation
- Lab
personnel:
- Sekar Nagaswami, MD - Research Specialist
Rustem Litvinov, PhD - Senior Research Investigator
Irina Chernysh, PhD - Research Specialist
Jim Torbet, PhD - Visiting Scholar
Nolan Shenai - Undergraduate Student
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last updated 9/2003 |
