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C. Forbes Dewey, Jr. Ph.D.

Department of Mechanical Engineering
Professor of Mechanical & Biological Engineering
Co-Director of the International Consortium for Medical Imaging Technology (ICMIT)

Room 3-254
617-253-2235 (phone)

Biosketch

B.E., Yale University, 1956
M.S. Stanford University, 1957
Ph.D. California Institute of Technology, 1963
Assistant Professor, University of Colorado, 1963-1968
Associate Professor, MIT, 1968-75
Professor of Mechanical Engineering, 1975-1998
Professor of Mechanical Engineering and Bioengineering, 1998-present

Research Summary

Understanding 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 and molecular biology to probe the fundamental mechanisms of this response. We hypothesize that the primary means of eliciting the response to flow is the shear force acting on a thin layer of glycosaminoglycans attached to the surface membrane of the cell with transmembrane molecular anchors. We are measuring the details of this process, and hope to determine the means by which some arteries are spared from atherosclerosis and others are susceptible to disease.  This work is being pursued with Prof. Guillermo Garcia-Cardena at the Brigham and Women’s Hospital, Harvard Medical School.

Computational Systems Biology

Since the sequencing of the human genome, biology has moved rapidly toward quantitative descriptions of the many interacting molecular process at the cell, tissue, and organ level.  This quantitative approach, both theoretical and experimental, is significantly altering the way in which basic medical research is carried out and, ultimately, how medicine is practiced. It also has the potential to revolutionise the way in which disease etiology is identified and modelled, and how possible cures are assayed for efficacy and toxicity. Systems biology has provided a new level of modelling that will effect every level of understanding of human disease.  We are developing new tools to capture this information in quantitative modelling methods that are designed to scale to very large assemblies of molecular pathways.  A new parallel computational method ahs recently been developed and is now available to the public (Cytosolve).   Two early targets of our research are a comprehensive model of NO production in endothelial cells and the death of cardiovascular muscle cells following ischemia and reperfusion. 

Selected Publications

  • Ayyadurai, V.A.S., and C.F. Dewey, Jr. 2009. A distributed computational architecture for integrating multiple biomolecular pathways. BMC Bioinformatics (in review).
  • Bindschadler, M., E.A. Osborn, C.F. Dewey, Jr., and J.L. McGrath. 2004. A mechanistic model of the actin cycle. Biophys J 86(5):2720-2739.
  • Cheng, Y., C.H. Hartemink, J.H. Hartwig, and C.F. Dewey, Jr. 2000. Three-dimensional reconstruction of the cell cytoskeleton from stereo images. J. Biomech. 33:105-113.
  • Dao, N., P.J. McCormick, and C.F. Dewey, Jr. 2000. The human physiome as an information environment. Annals of Biomedical Engineering 28:1032-1042.
  • Dao, N.D., and C.F. Dewey, Jr. 2009. A new class of functions for describing logical structures in text. Proc.National Academy of Sciences (in review).
  • Davies, P.F., C.F. Dewey, Jr., S.R. Bussolari, E.J. Gordon, and M.A. Gimbrone, Jr. 1984. Influence of hemodynamic factors on vascular endothelial function. J. Clin. Invest. 73:1121-1129.
  • Davies, P.F., A. Remuzzi, E.J. Gordon, C.F. Dewey, Jr., and M.A. Gimbrone, Jr. 1986. Turbulent fluid shear stress induces vascular endothelial turnover in vitro. Proc. Natl. Acad. Sci., U.S.A. 83:2114-2117.
  • DePaola, N., M.A. Gimbrone, Jr., P.F. Davies, and C.F. Dewey, Jr. 1992. Vascular Endothelium Responds to Fluid Shear Stress Gradients. Arteriosclerosis and Thrombosis 12:1254-1257.
  • Dewey, C.F., Jr. 1979. Dynamics of arterial flow. Adv. Exp. Med. Biol. 115:55-103.
  • Dewey, C.F., Jr., S.R. Bussolari, M.A. Gimbrone, Jr., and P.F. Davies. 1981. The dynamic response of vascular endothelial cells to fluid shear stress. J. Biomech. Eng. 103:177-185.
  • Dewey, C.F, Jr., J.D. Thomas, M. Kunt, and I.W. Hunter. 1996. Prospects for Telediagnosis Using Ultrasound. Telemedicine Journal 2:87-100.
  • Duncan, G.W., J.O. Gruber, C.F. Dewey, Jr., G.S. Myers, and R.S. Lees. 1975. Evaluation of carotid stenosis by phonoangiography. N Engl J Med 293(22):1124-1128.
  • Fillit, H.M., A.W. O'Connell, W.M. Brown, L.D. Altstiel, R. Anand, C. Collins, S.H. Ferris, Z.S. Khaturian, J., Kinoshita, L. Van Eldik, and C.F. Dewey, Jr. 2002. Barriers to drug discovery and development for Alzheimer disease. Alzheimer Disease and Associated Disorders 16:S1-S8.
  • Huang, H., Y. Yao, M. Cieselwicz, M. Bawendi, and C.F. Dewey, Jr. 2008. Three-dimensional sub-diffractionlimit tracking of proteins near the cell membrane: application to the endothelial glycocalyx. Proc.National Acad. Sci. [In press].
  • Jonas, M., Y. Yao, P.T.C. So, and C.F. Dewey, Jr. 2006. Detecting single quantum dot motion with nanometer resolution and application to cell biology. IEEE Transactions on Nanobiscience 5(4):246-250.
  • Lees, R.S., and C.F. Dewey, Jr. 1970. Phonoangiography: A new noninvasive diagnostic method for studying arterial disease. PNAS 67(October):935-942.
  • McGrath, J.L., J.H. Hartwig, Y. Tardy, and C.F. Dewey, Jr. 1998a. Measuring actin dynamics in endothelial cells. Microscopy Research and Technique 43:385-394.
  • McGrath, J.L., Y. Tardy, C.F. Dewey, Jr., J.J. Meister, and J.H. Hartwig. 1998b. Simultaneous measurements of actin filament turnover, filament fraction, and monomer diffusion in endothelial cells. Biophys. J.75:2070-2078.
  • McGrath, J.L., E.A. Osborn, C.F. Dewey, Jr., Y.S. Tardy, and J.H. Hartwig. 2000. Regulation of the actin cycle in vivo by actin filament severing. Proc. Nat. Acad. Sciences 97:6532-6537.
  • McGrath, J.L., and C.F. Dewey, Jr. 2006. Cytoskeletal Mechanics. In Cytoskeletal Mechanics. Mofrad MRK, Kamm RD, editors. Cambridge University Press, Cambridge, UK. 170-203.
  • Nagel, T., N. Resnick, W. Atkinson, C. Dewey, Jr., and M. Gimbrone, Jr. 1994. Shear stress selectively upregulates intercellular adhesion molecule-1 expression in cultured human vascular endothelial cells. J Clin Invest 94(2):885-891.
  • Nagel, T., N. Resnick, C.F. Dewey, Jr., and M.A. Gimbrone, Jr. 1999. Vascular endothelial cells respond to spatial gradients in fluid shear stress by enhanced activation of transcription factors. Arterioscler Thromb Vasc Biol 19(8):1825-1834.
  • Osborn, E., J.H. Hartwig, and C.F. Dewey, Jr. 2000. Fluid shear stress alters actin filament turnover and polymer fraction in endothelial cells. Annals of Biomedical Engineering 28 (Supplement 1):S-69.
  • Osborn, E.A., A. Rabodzey, C.F. Dewey, Jr., and J.H. Hartwig. 2006. Endothelial actin cytoskeleton remodeling during mechanostimulation with fluid shear stress. Am J Physiol Cell Physiol 290(2):C444-452.
  • Rabodzey, A., Y. Yao, J.H. Hartwig, F.W. Luscinskas, S.K. Shaw, and C.F. Dewey, Jr. 2007. Early response of endothelial cells to flow may be mediated by VE-cadherins. Cell Comm Adhesion 14(5):195-209.
  • Resnick, N., T. Collins, W. Atkinson, D.T. Bonthron, C.F. Dewey, Jr., and M.A. Gimbrone, Jr. 1993. Platelet derived growth factor B chain promoter contains a cis-acting fluid shear-stress-responsive element. Proc Natl Acad Sci U S A 90(10):4591-4595.
  • Satcher, R.L., Jr., S.R. Bussolari, M.A. Gimbrone, Jr., and C.F. Dewey, Jr. 1992. The distribution of fluid forces on model arterial endothelium using computational fluid dynamics. J. Biomech. Eng. 114:309-316.
  • Satcher, R.L., Jr., and C.F. Dewey, Jr. 1996. Theoretical estimates of mechanical properties of the endothelial cell cytoskeleton [see comments]. Biophys J 71(1):109-118.
  • Satcher, R.L., Jr., C.F. Dewey, Jr., and J.H. Hartwig. 1997. Mechanical remodeling of the endothelial surface and actin cytoskeleton induced by fluid flow. Microcirculation 4(4):439-453.
  • Shen, J., M. Gimbrone, A., Jr., F. Luscinskas, W., and C.F. Dewey, Jr. 1993. Regulation of adenine nucleotide concentration at endothelium-fluid interface by viscous shear flow. Biophys. J. 64:1323-1330.

 

Last Updated: March 25, 2010