John W. Weisel, Ph.D.

faculty photo
Professor of Cell and Developmental Biology
Department: Cell and Developmental Biology

Contact information
421 Curie Boulevard
Philadelphia, PA 19104-6058
Office: 215-898-3573
Fax: 215-898-9871
B.S. (Electrical Engineering)
Swarthmore College, 1968.
Ph.D. (Biophysics)
Brandeis University, 1973.
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Description of Research Expertise

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.

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.

Figure 1: Colorized scanning electron micrograph of a whole blood clot. Yuri Veklich and John Weisel.

Figure 2: Laser scanning confocal micrograph showing fibrinolysis of a platelet rich plasma blood clot. Reconstructed images at two different time points are shown in red and green to illustrate the changes that take place over time. Jean-Philippe Collet and John W. Weisel.

Rotation Projects for 2006-2007
1. Molecular mechanisms of platelet aggregation
2. Molecular mechanisms of fibrin assembly and fibrinolysis
3. Interactions of individual ligand-receptor pairs in vitro and on cells
4. Thrombus formation

Lab personnel:
Sekar Nagaswami, MD - Research Specialist
Rustem Litvinov, PhD - Senior Research Investigator
Irina Chernysh, PhD - Research Specialist
Zelda De Lange - Postdoctoral Fellow
Valerie Tutwiler - Graduate Student

Selected Publications

Litvinov, Rustem I. Yarovoi, Serge V. Rauova, Lubica. Barsegov, Valeri. Sachais, Bruce S. Rux, Ann H. Hinds, Jillian L. Arepally, Gowthami M. Cines, Douglas B. Weisel, John W.: Distinct specificity and single-molecule kinetics characterize the interaction of pathogenic and non-pathogenic antibodies against platelet factor 4-heparin complexes with platelet factor 4. Journal of Biological Chemistry 288(46): 33060-70, Nov 15 2013.

Kononova, Olga. Litvinov, Rustem I. Zhmurov, Artem. Alekseenko, Andrey. Cheng, Chia Ho. Agarwal, Silvi. Marx, Kenneth A. Weisel, John W. Barsegov, Valeri.: Molecular mechanisms, thermodynamics, and dissociation kinetics of knob-hole interactions in fibrin. Journal of Biological Chemistry 288(31): 22681-92, Aug 2 2013.

Eckmann, David M. Tsai, Irene Y. Tomczyk, Nancy. Weisel, John W. Composto, Russell J.: Hyaluronan and dextran modified tubes resist cellular activation with blood contact. Colloids & Surfaces B: Biointerfaces 108: 44-51, Aug 1 2013.

Weisel, John W. Litvinov, Rustem I.: Adaptation of fibrous biopolymers to recurring increasing strains. Proceedings of the National Academy of Sciences of the United States of America 110(30): 12164-5, Jul 23 2013.

Wang, Yanfeng. Zhao, Liang. Suzuki, Aae. Lian, Lurong. Min, Sang H. Wang, Ziqian. Litvinov, Rustem I. Stalker, Timothy J. Yago, Tadayuki. Klopocki, Arkadiusz G. Schmidtke, David W. Yin, Helen. Choi, John K. McEver, Rodger P. Weisel, John W. Hartwig, John H. Abrams, Charles S.: Platelets lacking PIP5KI have normal integrin activation but impaired cytoskeletal-membrane integrity and adhesion. Blood 121(14): 2743-52, Apr 4 2013.

Weisel, John W. Litvinov, Rustem I.: Mechanisms of fibrin polymerization and clinical implications. [Review] Blood 121(10): 1712-9, Mar 7 2013.

Hategan, Alina. Gersh, Kathryn C. Safer, Daniel. Weisel, John W.: Visualization of the dynamics of fibrin clot growth 1 molecule at a time by total internal reflection fluorescence microscopy. Blood 121(8): 1455-8, Feb 21 2013.

Zhmurov, Artem. Kononova, Olga. Litvinov, Rustem I. Dima, Ruxandra I. Barsegov, Valeri. Weisel, John W.: Mechanical transition from alpha-helical coiled coils to beta-sheets in fibrin(ogen). Journal of the American Chemical Society 134(50): 20396-402, Dec 19 2012.

Pieters, M. Undas, A. Marchi, R. De Maat, M P M. Weisel, J W. Ariens, R A S. Factor XIII And Fibrinogen Subcommittee Of The Scientific Standardisation Committee Of The International Society For Thrombosis And Haemostasis.: An international study on the standardization of fibrin clot permeability measurement: methodological considerations and implications for healthy control values. Journal of Thrombosis & Haemostasis 10(10): 2179-81, Oct 2012.

Litvinov, Rustem I. Mekler, Andrey. Shuman, Henry. Bennett, Joel S. Barsegov, Valeri. Weisel, John W.: Resolving two-dimensional kinetics of the integrin alphaIIbbeta3-fibrinogen interactions using binding-unbinding correlation spectroscopy. Journal of Biological Chemistry 287(42): 35275-85, Oct 12 2012.

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Last updated: 08/27/2014
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