In my laboratory we study the molecular mechanisms by which extracellular signals are transduced into effects on the cytoskeleton, and the consequence that these effects have on the development and function of neuronal cells in culture. We are currently examining the mechanisms by which signals such as membrane depolarization and substrate adhesivity modulate the polymerization and configuration of microtubules in neuronal growth cones, and the way in which these changes affect axonal and dendritic outgrowth. We use quantitative microsopic and image analysis of fluorescent tubulin and of fluorescent ion indicators to perform these studies in living cells, as they cannot yet be reconstructed outside of the cell. Results obtained are subsequently correlated with high resolution light and electron microscopic structural studies, and may allow us to determine the detailed mechanisms by which cell surface phenomena affect cell behavior.
In addition to the above biological projects, I have a rather general interest and expertise in biological instrumentation. I served as a Program Director for Biological Instrumentation at the National Science Foundation from 1993-1994, and am currently involved in the development of a robotics system for the physical mapping of fungal genomes, and in the development of novel microscopic and image processing techniques for studying biological phenomena.
M.A. Farmer and C.H. Keith. 2005. "Visualization of the Microtubules of Glutaraldehyde-Fixed Cells by Reflection-Enhanced Backscatter Confocal Microscopy" Microscopy and Microanalysis In Press.
Murnane, A.C, K. Brown, and C.H. Keith. 2002. "Preferential Initiation of PC12 Neurites in Directions of Changing Substrate Adhesivity." J. Neurosci. Res. 67:321-328.
Keith, C.H. and M.T. Wilson. 2001. "Factors Controlling Axonal and Dendritic Arbors." Internat. Rev. Cytol. 205: 77-147.
Kelkar, H.S., J. Griffith, M.E. Case, S.F. Covert, D.A. Hall, C. Keith, J.S. Oliver, M.J. Orbach, M.S. Sachs, J.R. Wagner, M.J. Weise, J.K. Wunderlich, and J. Arnold. 2001. "The Neurospora crassa genome: Cosmid libraries sorted by chromosome." Genetics 157: 979-990.
Keith, C.H., and R. Witek. 2001. "Enhancement of reflection-enhanced backscatter confocal microscopy." Microscopy and Microanalysis 7(1):1014-1015. (Reviewed abstract).
Wilson, M.T., W.S. Kisaalita, and C.H. Keith. 2000. "Glutamate-induced Changes in the Pattern of Hippocampal Dendrite Outgrowth: A Role for Calcium-Dependent Pathways and the Microtubule Cytoskeleton." J. Neurbiol. 43:159-172.
Keith, C.H., G.J. Bird, and M.A. Farmer. 1998. "Coherent Backscatter Enhances Reflection Confocal Microscopy." Biotechniques 25:858-866.
Wilson, M.T. and C.H. Keith. 1998. "Glutamate modulation of dendrite outgrowth: Alterations in the distribution of dendritic microtubules." J. Neurosci. Res. 52:599-611.
Agnihotri, N., W.S. Kisaalita, and C.H. Keith. 1997. "Free cyclic AMP increases in PC12 cells on depolarization." J. Neurosci. Res. 47:555-560.
Keith, C.H., and M.A. Farmer. 1993. "Microtubule behavior in PC12 neurites: Variable results obtained with photobleach technology." Cell Motil. Cytoskel. 25:345-357.
Reinach, P.S., R.R. Socci, C.H. Keith, and M. Scanlon. 1993. "Adrenergic receptor mediated increase of intracellular Ca2+ concentration in isolated bovine corneal epithelial cells." Comp. Biochem. and Physiol. 106:793-797.
Chu, T.C., C.H. Keith, E. Yee, and K. Green. 1992. "Intracellular pH of tissue-cultured bovine corneal endothelial cells." Ophthalmic Res. 24:265-273.
Low, H.P., J.J. Paulin, and C.H. Keith. 1992. "Trypanasoma cruzi infection of BSC-1 fibroblast cells causes cytoskeletal disruption and changes in intracellular calcium levels." J. Protozool. 49:463-470.
Keith, C.H. 1991. "Quantitative fluorescence techniques for the determination of local microtubule polymerization equilibria in cultured neurons." J. Neurosci. Meth.39:141-152.