C. Forbes Dewey, Jr.

Professor Dewey is a professor in the Mechanical Engineering Department and holds joint appointments in the Division of Biological Engineering and the Division of Health Sciences and Technology. He is also Co-Director of the International Consortium for Medical Imaging Technology (ICMIT) whose goal is the development and promotion of advanced technology for medical imaging.

Professor Dewey's research interests include fluids mechanics, cell dynamics and modeling, biomedical imaging, medical informatics, and instrumentation.

Research:

Probing the effects of mechanical forces on living cells
The primary medical problem that the Dewey research group investigates is atherosclerosis. The lumen of the arterial wall is lined with endothelial cells that respond to the mechanical forces of blood flowing through the arteries. The endothelium protects the artery wall from inflammatory reactions that result in atherosclerosis. Our lab was the first to demonstrate the time-course with which endothelial cells reorganize and reorient in the direction of fluid flow, and we continue to use microscopy to probe the fundamental mechanisms of this response. The mechanical structure of vascular endothelial cells depends on a network of polymerized actin molecules, and we use fluorescent dyes to track individual actin molecules as they diffuse through the cell.

In our in vitro model system, application of fluid shear force that is comparable to vascular blood flow in vivo induces a major transient decrease in polymerization. We believe that this alteration is correlated with the observed realignment of the cells in the flow direction. Measurements of cell motility and intercellular gap junction proteins are extending our understanding of the interaction process. This research is a collaborative effort with Prof. John Hartwig at the Brigham and Women's Hospital, Harvard Medical School.

As part of this project, we are collaborating with Prof. James McGrath at the University of Rochester to develop a computation model of actin polymerization. The ability to peer inside individual cells with modern fluorescence techniques has powered a profound change in our quantitative understanding of cellular biological function. For example, we reconstruct 3-dimensional images from stereo image pairs taken with a scanning electron microscopy (SEM). These images allow us to see the interaction of individual structural features within the cells at the molecular level – e.g, interactions between polymerized actin filaments and the actin binding protein filamin-A.

Integration of experimental data from different sources
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 data from all of the major experimental systems in a single ontological framework.

We have implemented this approach for gel electrophoresis, microarrays and fluorescence-activated cell sorting, demonstrating that data from these diverse sources can be stored and interrogated within a single database or an integrated network of databases. Currently we are incorporating mass spectrometry and optical microscopy into this system. This cross-disciplinary data integration effort is coordinated by the Interoperable Informatics Infrastructure Consortium (I3C), which was organized to promote and develop methodologies for data and tool interoperability in the life sciences, based on open and public specifications and protocols.

This work is based on a model that was pioneered by the International Consortium for Medical Information Technology (ICMIT), which we founded to develop and implement international data standards in medical imaging technologies such as magnetic resonance imaging (MRI), computerized axial tomography (CT) and X-rays. The Co-Director of the ICMIT is Prof. Richard Kitney of Imperial College in London.

Research Highlights:

Information Technology
      Actin Dynamics in Vascular Endothelium
      DICOM medical database
      Physiome project
      Medical information infrastructure
      Method of Indexing and Implicitly Discovering Document Logical Structures
      Educational project

Cellular Mechanics
      A comprehensive physiome of the heart
      Actin Dynamics in Motile Cells
      Biomedical image analysis
      Effects of fluid forces on vascular endothelium
      Studying the Nanostructure of the Actin Cytoskeleton

Post Doctoral Fellow:

Chan Young Park

Graduate Students:

Shiva Ayyadurai
Christopher Hartemink
Aleksandr Rabodzey
Yu Yao

Recent Alumni:

Yuan Cheng
William Chuang
Ngon Dao
Matthieu Ferrant (visiting student from UCL, Belgium)
James McGrath
Patrick McCormick
Eric Osborn
Maiya Shur
Kathleen Steinhoefel (visting scholar from the Fraunhofer Institute in Berlin, Germany.
Shixin (Jason) Zhang
Yoshihiro Yasumuro (visiting student from Naist, Japan)

Courses Taught:

2.671 - Measurement and Instrumentation
2.771J / BE.453J / HST.958J - Biomedical Information Technology
2.996 - Advance Topics in Mechanical Engineering

Recent Selected Publication:

1. Satcher RL JR, Bussolari SR, Gimbrone MA JR, Dewey CF JR. 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, Dewey CF JR. Interpreting Photoactivated Fluorescence Microscopy Measurements of Steady-State Actin Dynamics. Biophys. J. 1995;69:1674-1682.

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

4. Dewey CF JR. 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, Gimbrone MA JR, Dewey CF JR. 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 RL JR, Dewey CF JR, Hartwig JH. Mechanical Remodeling of the Endothelial Surface and Actin Cytoskeleton Induced by Fluid Flow. Microcirculation 1997; 4:439-453.

7. Dewey CF JR. 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. Dewey CF JR. 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 JR. 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, Dewey CF JR, 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 CF JR, Kitney RI. 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, Dewey CF JR. Measuring Actin Dynamics in Endothelial Cells. Microscopy Research and Technique 1998;43:385-394.

14. Nagel T, Resnick R, Dewey CF JR, Gimbrone MA 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 CF 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 JL, Osborn EA, Dewey CF Jr, Tardy YS, Hartwig JH. Regulation of the actin cycle in vivo by actin filament severing. Proc. Nat. Acad. Sciences 97, 6532-6537 (2000).

18. Dewey CF JR, Fu B, Zhang S, Dao N, Chuang W, 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 CF JR. Haemodynamic flow: symmetry and synthesis. Biorheology 39, 541-549 (2002).

21. Dewey CF JR, Zhang SA. Unique Opportunity in Biological Information Object Standards. Invited talk, 2003 World Congress on Medical Physics and Biomedical Engineering, August, 2003, Sydney.