John W. Weisel

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, Weisel John W: Fibrin mechanical properties and their structural origins. Matrix biology : journal of the International Society for Matrix Biology 60-61: 110-123, Jul 2017.

Kononova Olga, Litvinov Rustem I, Blokhin Dmitry S, Klochkov Vladimir V, Weisel John W, Bennett Joel S, Barsegov Valeri: Mechanistic Basis for the Binding of RGD- and AGDV-Peptides to the Platelet Integrin αIIbβ3. Biochemistry 56(13): 1932-1942, Apr 2017.

Silvain Johanne, Collet Jean-Philippe, Guedeney Paul, Varenne Olivier, Nagaswami Chandrasekaran, Maupain Carole, Empana Jean-Philippe, Boulanger Chantal, Tafflet Muriel, Manzo-Silberman Stephane, Kerneis Mathieu, Brugier Delphine, Vignolles Nicolas, Weisel John W, Jouven Xavier, Montalescot Gilles, Spaulding Christian: Thrombus composition in sudden cardiac death from acute myocardial infarction. Resuscitation 113: 108-114, Apr 2017.

Tutwiler Valerie, Wang Hailong, Litvinov Rustem I, Weisel John W, Shenoy Vivek B: Interplay of Platelet Contractility and Elasticity of Fibrin/Erythrocytes in Blood Clot Retraction. Biophysical journal 112(4): 714-723, Feb 2017.

Tutwiler Valerie, Peshkova Alina D, Andrianova Izabella A, Khasanova Dina R, Weisel John W, Litvinov Rustem I: Contraction of Blood Clots Is Impaired in Acute Ischemic Stroke. Arteriosclerosis, thrombosis, and vascular biology 37(2): 271-279, Feb 2017.

Litvinov Rustem I, Weisel John W: Role of red blood cells in haemostasis and thrombosis. ISBT science series 12(1): 176-183, Feb 2017.

Galanakis Dennis K, Spitzer Eric D, Perrotta Peter, Nagaswami Chandrasekaran, Marchi Rita, Spitzer Silvia, Refailovich Miriam, Smith Roy E, Zhang Liudi, Marmorat Clement, Weisel John W: Thrombosis-associated antifibrinogen IgG1 κ impairs fibrin polymerization and enhances platelet activation. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 28(1): 40-49, Jan 2017.

Weisel John W, Litvinov Rustem I: Fibrin Formation, Structure and Properties. Sub-cellular biochemistry 82: 405-456, 2017.

Cuker Adam, Husseinzadeh Holleh, Lebedeva Tatiana, Marturano Joseph E, Massefski Walter, Lowery Thomas J, Lambert Michele P, Abrams Charles S, Weisel John W, Cines Douglas B: Rapid Evaluation of Platelet Function With T2 Magnetic Resonance. American journal of clinical pathology 146(6): 681-693, Dec 2016.

Zhmurov Artem, Protopopova Anna D, Litvinov Rustem I, Zhukov Pavel, Mukhitov Alexander R, Weisel John W, Barsegov Valeri: Structural Basis of Interfacial Flexibility in Fibrin Oligomers. Structure (London, England : 1993) 24(11): 1907-1917, Nov 2016.

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Last updated: 12/04/2017
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