Biological Science Faculty Member
Dr. Thomas C. S. Keller
- E-mail: firstname.lastname@example.org
Ph.D., University of Virginia, 1981
Research and Professional Interests:
Our recent research investigated the roles that various cytoskeletal proteins play in the structure and function of nonmuscle cells.We focused our interest on a cellular isoform of the muscle protein titin that we discovered in the brush border. Titins are the largest ribosome-translated peptides found to date. In muscle, titin plays a key role in establishing and maintaining the integrity of the contractile sarcomere unit through interaction with the myosin thick filaments. Minititins found in invertebrates also appear to play a regulatory role in muscle contraction through an intrinsic kinase activity. Using immunofluorescence microscopy with an antibody that we raised against cellular titin, we have found cellular titin colocalized with myosin filaments in the brush border and in the stress fibers and cleavage furrows in all other cells that we have investigated. Our biochemical investigations of proteins purified from brush borders have revealed that cellular titin has the capability of organizing myosin filaments in vitro into arrays that with electron microscopy appear similar to those found in vivo. This finding indicates that cellular titin may play a key organizational role in important cytoskeletal assemblies in all cells. We have investigated the interaction of titin with several other cytoskeletal proteins including alpha-actinin.
We also investigate interaction of a variety of cell types with polyelectrolyte multilayer surfaces (PEMUs) in collboration with the Dr. Joe Schlenoff lab in the FSU Department of Chemistry and Biochemistry. PEMUs have tyunable properties and are protentially useful as biocompatible coatings for implantable medical devices. Our work focuses on determining how PEMUs influence adult the adhesion and migration of a variety of other cell types. Most recently. we have developed a protocol for preparing decellularized ECM-PEMU substrates that control adult stem cell stemness and differentiation.
Eilertsen, K., and T. Keller. 1992. Identification and characterization of two huge proteins of the brush border cytoskeleton: evidence for a cellular isoform of titin. J. Cell Biol. 119: 549-557.
Eilertsen, K., S. Kazmierski, and T. Keller. 1994. Cellular titin-myosin interaction: in vitro assembly and isoform specificity. J. Cell Biol. 126: 1201-1210.
Keller, T. 1995. Structure and function of titin and nebulin. Curr. Opinion Cell Biol. 7: 32-38.
Eilertsen, K. E., S. T. Kazmierski, and T. Keller. 1997. Interaction of alpha-actinin with cellular titin. Eur. J. Cell Biol. 74: 361-364.
Keller, T. 1997. Muscle structure: molecular bungees. Nature 387: 233-235.Kim, K., and T. Keller. 2002. Smitin, a novel smooth muscle titin-like protein, interacts with myosin filaments in vivo and in vitro. J. Cell Biol. 156: 101-111.
Salloum, D., Olenych, S., Keller, T., and Schlenoff, J. 2005. Vascular smooth muscle cells on polyelectrolyte multilayers: hydrophobicity-directed adhesion and growth. Biomacromolecules, 6, 161–167.
Olenych, S. G., Moussallem, M. D., Salloum, D. S., Schlenoff, J. B. and T. Keller. 2005. Fibronectin and cell attachment to cell and protein resistant polyelectrolyte surfaces. Biomacromolecules, 6, 3252–3258.
Chi, R. J., Olenych, S. G., Kim, K. T. and T. Keller. 2005. Smooth muscle α-actinin interaction with smitin. International Journal of Biochemistry and Cell Biology, 37, 1470–1482.
Cavnar, P. J., Olenych, S. G. and T. Keller. 2007. Molecular identification and localization of cellular titin, a novel titin isoform in the fibroblast stress fiber. Cell Motility and the Cytoskeleton, 64, 418–433.
Chi, R. J., Simon, A. R., Bienkiewicz, E. and T. Keller. 2008. Smooth muscle titin Zq domain interaction with the smooth muscle alpha-actinin central rod. Journal of Biological Chemistry, 283, 20959–20967.
Moussallem, M. D., Olenych, S. G., Scott, S. L., Keller, T. and J. Schlenoff, J. B. 2009. Smooth muscle cell phenotype modulation and contraction on native and cross-linked polyelectrolyte multilayers. Biomacromolecules, 10, 3062–3068.
Martinez, J. S., Keller, T. and J. Schlenoff. 2011. Cytotoxicity of free versus multilayered polyelectrolytes. Biomacromolecules, 12, 4063–4070.
Martinez, J., Lehaf, A., Schlenoff, J. and T. Keller. 2013. Cell durotaxis on polyelectrolyte multilayers with photogenerated gradients of modulus. Biomacromolecules, 14(5):1311-20.