Cell & Developmental Biology
faculty photo

John W. Weisel, Ph.D.

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

Contact information
1154 BRB II/III
421 Curie Boulevard
Philadelphia, PA 19104-6058
Office: 215-898-3573
Fax: 215-898-9871
Education:
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

Le Minh Giang, Peshkova Alina D, Andrianova Izabella A, Sibgatullin Timur B, Maksudova Adelia N, Weisel John W, Litvinov Rustem I: Impaired contraction of blood clots as a novel prothrombotic mechanism in systemic lupus erythematosus. Clinical science (London, England : 1979) 132(2): 243-254, Jan 2018.

Vostal Jaroslav G, Buehler Paul W, Gelderman Monique P, Alayash Abdu I, Doctor Alan, Zimring James C, Glynn Simone A, Hess John R, Klein Harvey, Acker Jason P, Spinella Philip C, D'Alessandro Angelo, Palsson Bernhard, Raife Thomas J, Busch Michael P, McMahon Timothy J, Intaglietta Marcos, Swartz Harold M, Dubick Michael A, Cardin Sylvain, Patel Rakesh P, Natanson Charles, Weisel John W, Muszynski Jennifer A, Norris Philip J, Ness Paul M: Proceedings of the Food and Drug Administration's public workshop on new red blood cell product regulatory science 2016. Transfusion 58(1): 255-266, Jan 2018.

Xu Shixin, Xu Zhiliang, Kim Oleg V, Litvinov Rustem I, Weisel John W, Alber Mark: Model predictions of deformation, embolization and permeability of partially obstructive blood clots under variable shear flow. Journal of the Royal Society, Interface 14(136), Nov 2017.

Kim Oleg V, Litvinov Rustem I, Alber Mark S, Weisel John W: Quantitative structural mechanobiology of platelet-driven blood clot contraction. Nature communications 8(1): 1274, Nov 2017.

Höök Peter, Litvinov Rustem I, Kim Oleg V, Xu Shixin, Xu Zhiliang, Bennett Joel S, Alber Mark S, Weisel John W: Strong Binding of Platelet Integrin αIIbβ3 to Fibrin Clots: Potential Target to Destabilize Thrombi. Scientific reports 7(1): 13001, Oct 2017.

Protopopova Anna D, Litvinov Rustem I, Galanakis Dennis K, Nagaswami Chandrasekaran, Barinov Nikolay A, Mukhitov Alexander R, Klinov Dmitry V, Weisel John W: Morphometric characterization of fibrinogen's αC regions and their role in fibrin self-assembly and molecular organization. Nanoscale 9(36): 13707-13716, Sep 2017.

Liang Xiaojun, Chernysh Irina, Purohit Prashant K, Weisel John W: Phase transitions during compression and decompression of clots from platelet-poor plasma, platelet-rich plasma and whole blood. Acta biomaterialia 60: 275-290, Sep 2017.

Bannish Brittany E, Chernysh Irina N, Keener James P, Fogelson Aaron L, Weisel John W: Molecular and Physical Mechanisms of Fibrinolysis and Thrombolysis from Mathematical Modeling and Experiments. Scientific reports 7(1): 6914, Aug 2017.

Höök Peter, Brito-Robinson Teresa, Kim Oleg, Narciso Cody, Goodson Holly V, Weisel John W, Alber Mark S, Zartman Jeremiah J: Whole blood clot optical clearing for nondestructive 3D imaging and quantitative analysis. Biomedical optics express 8(8): 3671-3686, Aug 2017.

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.

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Last updated: 12/04/2017
The Trustees of the University of Pennsylvania
 

Department of Cell and Developmental Biology
1150 BRB II
421 Currie Boulevard
Philadelphia, PA 19104
Tel: (215) 573-9306
Fax: (215) 898-9871