Research

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. Fluorescent dyes are used as markers to tag individual molecules of actin, and we look at how they move and diffuse through the cell. This can tell us how much of the actin is polymerized and how much is in monomeric form. Application of a fluid shear force comparable to those that blood flow applies to these cells causes a major transient decrease in polymerization, and we believe that this is correlated with the observed realignment of the cells in the flow direction. Additional measurements of cell motility and intercellular gap junction proteins is extending our understanding of the interaction process. We are also undertaking major computational modeling of actin polymerization in collaboration with colleagues at the University of Rochester. The ability to peer inside individual cells with modern fluorescence techniques has powered a profound change in our quantitative understanding of cellular biological function. Our imaging research also includes the reconstruction of 3-D images from stereo pairs taken using scanning electron microscopy (SEM). These images allow us to see the interaction of individual structural features within the cells at the molecular level. We currently use antibodies tagged with gold particles to visualize the specific conformation and interaction between different proteins, for example between polymerized actin filaments and the actin binding protein filamin-A.

A second major program within the lab is the development of robust information systems for biological data. Our goal is to develop a common technology that will capture all major experimental biological data types in a single ontological framework. So far, we have shown this with gel electrophoresis, microarrays, and fluorescence-activated cell sorting, and are currently implementing mass spectrometry and optical microscopy. We've shown that these data can all be stored and searched from within a single database or from collaborating (federated) databases. The methods of federation are novel and have significant potential for application. A second area of research is the development of new algorithms for extracting structured information from unstructured documents. Additional information on these results will be available in the Fall of 2003.

Selected Publications

1. 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.

2. 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.

3. Dewey J, C. F., Thomas JD, Kunt M, Hunter IW. Prospects for Telediagnosis Using Ultrasound. Telemedicine Journal 1996;2:87-100.

4. Virtual Files: The Key to Managing Medical Images (Abstract). Ann. Proc. Fall Meeting of Biomedical Engineering Society; 1996.

5. 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.

6. 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.

7. Extending Dicom Databases to New Imaging Modalities (Abstract). Proc. World Congress on Medical Physics and Biomedical Eng.; 1997 Sept. 14-19, 1997; Nice, France.

8. 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.

9. Dao N, Dewey CF. Databasing Strategy for the Human Physiome, (Abstract). Ann Biomed. Eng'g 1998;26 (Suppl. 1), S-13.

10. 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.

11. 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.

12. 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.

13. McGrath JL, Hartwig J, Tardy Y, C. F. Dewey J. Measuring Actin Dynamics in Endothelial Cells. Microscopy Research and Technique 1998;43:385-394.

14. 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).

15. Dao, N., McCormick, P. J. & Dewey, C. F., Jr. The human physiome as an information environment. Annals of Biomedical Engineering 28, 1032-1042 (2000).

16. 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).

17. 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).

18. 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.

19. Fillit, H. et al. Barriers to Drug Discovery and Development for Alzheimer Disease. Alzheimer Disease and Associated Disorders 16, S1-S8 (2002).

20. Dewey, C. F., Jr. Haemodynamic flow: symmetry and synthesis. Biorheology 39, 541-549 (2002).

21. 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.

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