Thomas Egelhoff Ph.D.

Staff

  • Department of Cellular and Molecular Medicine
  • Lerner Research Institute
  • 9500 Euclid Avenue
  • Cleveland, Ohio 44195
  • egelhot@ccf.org
  • Phone: (216) 445-9912
  • Fax: (216) 444-9404

Research in the Egelhoff lab focuses on dissecting the cellular machinery that drives cell migration and invasion, with emphasis on understanding the roles and regulation of myosin II.  Studies in the lab are currently focused on understanding myosin II functions and regulation during cancer progression and invasive migration by cancer cells.  We recently discovered novel and dramatic regulation of myosin II expression and activation when mammary gland epithelial cells respond to the cytokine TGFß - a stimulus that promotes epithelial-to-mesenchymal-transition (EMT).  These studies have revealed a critical role for specific myosin II isoforms in invasive migration in breast epithelial cells and in breast cancer cells, a role that we are currently trying to understand at the cellular and biophysical levels. 

We use an array of biochemical, cellular, and live cell imaging approaches in our work, with emphasis on dynamic reporter tools such as GFP fusions and fluorescent recovery after photobleaching (FRAP).  We use an array of biophysical tools to understand cellular force production, such as cellular responses in engineered microfluidics chemotaxis chambers, engineered “tunable” migration substrates where microenvironment stiffness can be controlled, and use of fluorescent-bead impregnated flexible migration substrates that allow quantitation of cellular force production with micron resolution. 

To implement these approaches and apply them to clinically relevant questions, we have engaged a team of ongoing collaborators that include biomedical engineers, biophysicists, and clinical pathologists.  These collaborations facilitate a unique, innovative, and interdisciplinary approach to our studies.

In other words ...

The Egelhoff lab studies the mechanical structures inside cells that drive cell migration.  "Nanoscopic" scaffold-like structures in cells assemble, disassemble, and relocalize continuosly as cell migrate, and these structures produce force to help cells squeeze through tight spaces.  Our studies have demonstrated that abundance of these  scaffold structures is strongly increased when cancer cells become metastatic, and in skin cells during wound healing.  In both cases, the increased abundance of these proteins drives invasive cell migration.  We seek to understand how cells upregulate expression of these proteins- in the case of metastasis, our studies could potentially lead to new ways to block cancer metastasis.  In the case of skin wound healing, we may ultimately be able to enhance wound healing by manpulation of these scaffolding structures.

  • Vandana Rai PhD
  • Postdoctoral Fellow
  • Location:NC1-145
  • Phone:(216) 445-9913
  • Fax:(216) 444-9404
  • raiv@ccf.org
  • Dustin Thomas
  • Graduate Student
  • Location:NC1-145
  • Phone:(216) 445-9913
  • Fax:(216) 444-9404
  • thomasd17@ccf.org

Myosin II Isoform Switching Mediates Invasiveness following TGFβ-induced Epithelial-Mesenchymal Transition.  Beach, J.R., George S. Hussey, G.S., Miller, T.E., Chaudhury,A., Patel, P., Monslow,J., Zheng,Q., Keri, R.A., Reizes, O., Bresnick, A.R., Howe, P.H., Egelhoff, T.T.  PNAS.  108:17991-6, 2011.  

Role of B regulatory subunits of PP2A in myosin II assembly control in Dictyostelium discoideum.  Rai, V. and Egelhoff, T. T.  Eukaryotic Cell, 10:604-610, 2011.  

A proteomic study of myosin II motor proteins during tumor cell migration.  Betapudi, V., Gokulrangan, G., Chance, M.R., and Egelhoff, T.T.  Journal of Molecular Biology, 407:673-686, 2011 

A microfluidic imaging chamber for the direct observation of chemotactic transmigration.  Breckenridge, M.T., Egelhoff, T.T., and Baskaran, H. Biomedical Microdevicies, 12:543-53.  2010. 

Search PubMed for articles by Dr. Egelhoff