Biography

I am developing new smart medical adhesives by utilizing biological adhesive molecules that can be triggered to bind or dissociate. I am also developing and using new instruments to study the biophysics of adhesive molecules involved in infection and thrombosis.

I am interested in the regulation of biological adhesion. Our major focus is on catch bonds, which are biological adhesive bonds that are activated by mechanical force. We study the biophysics of catch bonds that are involved in blood clotting and in bacterial infections. We hope that some of these projects will help us to better understand arterial thrombosis, with the long term role of developing new drugs that will prevent heart attacks and strokes without causing so much bleeding. In other projects, we hope to develop new antiadhesive therapies for urinary tract infections and endocarditis, hoping that these new approaches will not cause antibiotic resistance. Like a nanoscale locking seatbelt, catch bonds bind when needed but allow movement at other times, which makes them exciting new tools for adhesive technology that can be used in biosensing, molecular imaging, point-of-care diagnostics, targeted drug delivery, or minimally invasive microrobotics.

To study the biophysics of catch bonds, we apply and develop engineering tools such as single molecule biophysics instrumentation. We also study the role of catch bonds in cell adhesion by using integrative simulations to relate nanoscale to microscale behaviors, and by using site-directed mutagenesis to change molecular properties so we can see how the cell behavior changes. To develop new adhesive technology, we use the biophysics tools we have developed to predict and characterize desired properties for different applications. We also use protein engineering tools including RosettaDesign and directed evolution to engineer proteins with the desired properties.

Education

• PhD, Bioengineering, University of Washington, 2003
• MS, Applied Mathematics, University of Washington 2003
• AB, Molecular Biology, Princeton University 1987

Previous appointments

• Postdoctoral Fellow, Bioengineering, University of Washington, 2003-2004

Select publications

1. Interlandi, G. and W.E. Thomas. “Mechanism of allosteric propagation across a β-sheet structure investigated by molecular dynamics simulations,” Proteins 84 p. 990-1008 (April 2016)
2. Tronic, E.H., O. Yakovenko, T. Weidner, J.E. Baio, R. Penkala, D.G. Castner, and W.E. Thomas, “Differential surface activation of the A1 domain of von Willebrand factor,” Biointerphases, 11 029803 (March 2016)
3. Yakovenko, O., V. Tchesnokova, E.V. Sokurenko, W.E. Thomas, “Inactive conformation enhances binding function in physiological conditions,” PNAS 112, p. 9884-9889 (Aug 2015)
4. Kisiela D.I., H. Avagyan, A. Jalan, S. Gupta, G. Interlandi, Y. Liu, V. Tchesnokova, V.B. Rodriguez, X. Wu, W.E. Thomas, and E.V. Sokurenko, “Inhibition and reversal of microbial attachment by antibody with parasteric activity against FimH adhesin, the vaccine target against uropathogenic E. coli”, PLoS Pathogens 11 p. e1004857 (May 2015).
5. Whitfield, M.J., J.P. Luo, W.E. Thomas, “Yielding Elastic Tethers Stabilize Robust Cell Adhesion,” PLoS Computational Biology 10, p. e1002371 (Dec 2014)
6. Kisiela, D.I., V.B. Rodriguez, V. Tchesnokova, H. Avagyan, P. Aprikian, Y. Liu, X.R. Wu, W.E. Thomas, E.V. Sokurenko, “Conformational inactivation induces immunogenicity of the receptor-binding pocket of a bacterial adhesin” PNAS 110, p. 19089-94 (Nov 2013)
7. Rodriguez, V.B, B.A. Kidd, G. Interlandi, V. Tchesnokova, E.V. Sokurenko, W.E. Thomas, “Allosteric Coupling in the Bacterial Adhesive Protein FimH”, J. Biol Chem 288 (33), 24128-39 (July 2013)
8. Liu, Y., Esser, L., Interlandi, G., Kisiela, D. I., Tchesnokova, V., Thomas, W. E., Sokurenko, E., Xia, D., Savarino, S. J., “Tight Conformational Coupling between the Domains of the Enterotoxigenic Escherichia coli Fimbrial Adhesin CfaE Regulates Binding State Transition,” J Biol Chem, 288, p. 9993-10001 (Feb 2013)
9. Interlandi, G, M. Ling, A.Y. Tu, D. W. Chung, and W. E. Thomas, “Structural basis of type 2A von Willebrand disease investigated by molecular dynamics simulations and experiments”PLoS One, 7, p. e45207 (Oct 2012)
10. Tchesnokova V., P. Aprikian, D. Kisiela, S. Gowey, N. Korotkova, W. Thomas, E. Sokurenko, “Type 1 fimbrial adhesin FimH elicits immune response which enhances cell adhesion of Escherichia coli” Infection and Immunity, 79, p. 3895-3904 (Oct 2011)
11. Aprikian, P, G. Interlandi, B. Kidd, I. Le Trong, V. Tchesnokova, O. Yakovenko, M. Whitfield, E. Bullitt, R. Stenkamp, W.E. Thomas, E.V. Sokurenko, “The Bacterial Fimbrial Tip Acts as a Mechanical Force Sensor” PLoS Biology, (May 2011) 9, p. e1000617
12. Whitfield, M, W.E. Thomas*, “A nanoadhesive composed of receptor-ligand bonds”, Journal of Adhesion, in press
13. W.E. Thomas*, D.E. Discher*, Prasad Shastri*, “Mechanical regulation of cells by materials and tissues”, MRS Bulletin, 35 p. 578-583 (2010).
14. Whitfield MJ, Ghose T, Thomas WE, “The shear-stabilized rolling behavior of E. coli examined with simulations.” Biophysical Journal, 99, p. 2470-78 (2010)
15. Le Trong I, Aprikian P, Kidd BA, Thomas WE, Sokurenko EV, Stenkamp RE, “Donor strand exchange and conformational changes during E. coli fimbrial formation.” Journal of Structural Biology, 172, p. 380-88 (2010)
16. Interlandi G, Thomas WE, “The catch bond mechanism between von Willebrand Factor and platelet surface receptors investigated by molecular dynamics simulations” Proteins 78 p. 2506-22 (Aug 2010)
17. Bao, G, Kamm RD, Thomas W, Hwang W, Fletcher DA, Grodzinsky AJ, Zhu C, Mofrad MRK “Molecular Biomechanics: The Molecular Basis of How Forces Regulate Cellular Function.” Cellular and Molecular Bioengineering 3 p 91-105 (June 2010)
18. Le Trong I, Aprikian P, Kidd BA, Forero-Shelton M, Tchesnokova V, Rajagopal P, Rodriguez V, Interlandi G, Klevit R, Vogel V, Stenkamp RE, Sokurenko EV, Thomas WE, “Structural basis for mechanical force regulation of the adhesin FimH via finger trap-like beta sheet twisting” Cell 141 p 645-55 (May 2010) (NIHMS version free text)
19. Tchesnokova V, McVeigh AL, Kidd B, Yakovenko O, Thomas WE, Sokurenko EV, Savarino SJ, “Shear-enhanced binding of intestinal colonization factor antigen I of enterotoxigenic Escherichia coli” Molecular Microbiology 76 p 489-502 (April 2010)
20. Kidd BA, Baker D*, and Thomas WE* “Computation of Conformational Coupling in Allosteric Proteins” PLoS computational Biology 5 p e1000484 (Aug 2009)
21. Thomas, WE*. Mechanochemistry of receptor-ligand bonds. Current Opinion in Structural Biology (2009)

Honors & awards

• 2016: University of Washington Undergraduate Research Mentor Award
• 2016: University of Washington Distinguished Teaching Award
• 2016: University of Washington College of Engineering Faculty Teaching Award
• 2007-2010: BMES Board of Directors
• 2007: American Heart Association National Scientist Development Grant
• 2007: National Science Foundation CAREER Award
• 1999-2003: Whitaker Foundation Graduate Fellowship
• 2017: Fellow, American Institute of Medical and Biological Engineering (AIMBE)