C. Forbes Dewey, Jr., Ph.D.
Professor of Mechanical Engineering and Biological Engineering
Research group web site
Phone: (617) 253-2235
Fax: (617) 258-8559
Administrative Assistant: Sean Buhrmester
Courses: 2.671, 2.771J/20.453J/HST.958J, 2.996
My research group uses microscopy to probe the effects of mechanical forces on living cells. Our targets of interest, endothelial cells, protect the artery wall from the inflammatory reactions that result in atherosclerosis. The cells have a mechanical structure that depends on a network of polymerized actin molecules, and they are covered with a layer of glycosaminoglycans of around 400 nm in thickness, called the Endothelial Glycocalyx layer (EGL). The EGL is a major determinant of their state and theor interactions with external flow. Fluorescent dyes are used as markers to tag individual molecules of actin, NO, VE Cadherin, Heparin Sulfate and other molecules that are important to cellular function and biological response. Our current focus is on the EGL, and we are using super-resolution optical imaging to track the motion of EGL structures to better than 15 nm in three dimensions. These measurements provide information on the mechanical properties of the EGL, and will lead to theoretical estimates of how the EGL is distorted by blood flow and hopefully reveal the fundamental mechanisms of how mechanical force is transduced into biochemical signals.
We are also undertaking a major development program to create a new computational modeling environment where experimental data can be correlated using quantitative molecular modeling across a diverse number of individual experiments. This work has produced a new program called Cytosolve that is capable of solving a very large number of molecular pathway models simultaneously. The architecture allows the complexity to grow linearly with the number of models, in contrast to the literally unscaleable methods that have been proposed in the past. Early example applications have been extremely encouraging, and this effort is poised for expansion.
Satcher J, R. L., Bussolari SR, M. A. Gimbrone J, C. F. Dewey J. The Distribution of Fluid Forces on Model Arterial Endothelium Model Arterial Endothelium Using Computational Fluid Dynamics. J. Biomechanical Engineering 1992;114:309-316.
Tardy Y, McGrath JL, Hartwig JH, C. F. Dewey J. Interpreting Photoactivated Fluorescence Microscopy Measurements of Steady-State Actin Dynamics. Biophys. J. 1995;69:1674-1682.
Dewey J, C. F., Thomas JD, Kunt M, Hunter IW. Prospects for Telediagnosis Using Ultrasound. Telemedicine Journal 1996;2:87-100.
Virtual Files: The Key to Managing Medical Images (Abstract). Ann. Proc. Fall Meeting of Biomedical Engineering Society; 1996.
Tardy Y, Resnick N, Nagel T, M. A. Gimbrone J, C. F. Dewey J. Shear Stress Gradients Remodel Endothelial Monolayers in Vitro Via a Cell Proliferation-Migration-Loss Cycle. Arterios., Thromb., & Vasc., Biol. 1997;17:3102-3106.
Satcher, R.L., Dewey, C.F. Jr., and Hartwig, J.H. Mechanical Remodeling of the Endothelial Surface and Actin Cytoskeleton Induced by Fluid Flow. Microcirculation 1997; 4:439-453.
Extending Dicom Databases to New Imaging Modalities (Abstract). Proc. World Congress on Medical Physics and Biomedical Eng.; 1997 Sept. 14-19, 1997; Nice, France.
An Object-Relational Architecture for a Dicom Medical Image Archive (Abstract). Proc. World Congress on Medical Physics and Biomedical Eng.; 1997 Sept. 14-19, 1997; Nice, France.
Dao N, Dewey CF. Databasing Strategy for the Human Physiome, (Abstract). Ann Biomed. Eng'g 1998;26 (Suppl. 1), S-13.
Dao N, Dewey CF, Jr. Design and Prototype of a Database for Medical Images, (Abstract). Ann. Biomed. Eng'g 1998;26 (Suppl. 1):S-13.
McGrath JL, Tardy Y, C. F. Dewey J, Meister JJ, Hartwig JH. Simultaneous Measurements of Actin Filament Turnover, Filament Fraction, and Monomer Diffusion in Endothelial Cells. Biophys. J. 1998;75:2070-2078.
Dewey, C.F. Jr., Kitney, R.I. Creating DICOM-Enabled Clinical Systems with Robust Image-Querying Capabilities. Proc. Towards An Electronic Patient Record '98; C. P. Waegemann, editor. 1998 May 9-15, 1998; San Antonio, TX. Medical Records Institute.
McGrath JL, Hartwig J, Tardy Y, C. F. Dewey J. Measuring Actin Dynamics in Endothelial Cells. Microscopy Research and Technique 1998;43:385-394.
Nagel, T., Resnick, R., Dewey, C.F. Jr., and Gimbrone, M.A. Jr. Vascular Endothelial Cells Respond to Spatial Gradients in Fluid Shear Stress by Enhanced Activation of Transcription Factors, Arteriosclerosis, Thrombosis, and Vasc. Biol. 19, 1825-1834 (1999).
Dao, N., McCormick, P. J. & Dewey, C. F., Jr. The human physiome as an information environment. Annals of Biomedical Engineering 28, 1032-1042 (2000).
Cheng Y, Hartemink C, Hartwig JH, Dewey CF, Jr. Three Dimensional Reconstruction of the Cell Cytoskeleton from Stereo Images. J. Biomechanics 33, 105-113 (2000).
McGrath, J. L., Osborn, E. A., Dewey, C. F., Jr., Tardy, Y. S. & Hartwig, J. H. Regulation of the actin cycle in vivo by actin filament severing. Proc. Nat. Acad. Sciences 97, 6532-6537 (2000).
Dewey, C.F. Jr., Fu, B., Zhang, S., Dao, N., Chuang, W., and Li, Z.. An information architecture for physiological models, clients, and databases. Proc. IEEE-EMBS European Conference on Medical and Biological Systems, October, 2001, Istanbul.
Fillit, H. et al. Barriers to Drug Discovery and Development for Alzheimer Disease. Alzheimer Disease and Associated Disorders 16, S1-S8 (2002).
Dewey, C. F., Jr. Haemodynamic flow: symmetry and synthesis. Biorheology 39, 541-549 (2002).
Dewey, C.F.Jr., and Zhang, S. A Unique Opportunity in Biological Information Object Standards. Invited talk, 2003 World Congress on Medical Physics and Biomedical Engineering, August, 2003, Sydney.