References:
- Morris, A. P., Cunningham, S. A., Benos, D. J., and Frizzell, R. A. Cellular differentiation is required for cAMP but not Ca2+ dependent Cl- secretion in colonic epithelial cells expressing high levels of CFTR. J. Biol. Chem. 267:5575-5583, 1992.
- Morris, A. P., Kirk, K. L., and R.A. Frizzell, R. A. Simultaneous analysis of cell Ca2+ and Ca2+-stimulated chloride conductance in colonic epithelial cell (HT29). Cell Regulation 1(12): 953-963, 1990.
- Morris, A. P., Gallacher, D. V., Irvine, R. F., and Petersen, O. H. Synergism of Ins(1,4,5)P3 with Ins(1,3,4,5)P4 in activating Ca-dependent channels. Nature 330:653-655, 1987.
Andrew P. Morris, Ph.D.
Associate Professor
UTHSC, Medical School, (713) 500 - 6681
Andrew.P.Morris@uth.tmc.edu
Epithelial polarity and ion channel trafficking
The cellular mechanisms leading to the attainment and maintenance of membrane asymmetry (cellular polarization) is of major interest to epithelial cell biologists and physiologists. This is because the ability of an epithelium to secrete or absorb fluid is intimately linked to the asymmetrical distribution of plasma membrane-bound proteins responsible for transepithelial ion movement (ion channels, cotransporters and pumps). My laboratory is interested in cellular factors that facilitate apical membrane vesicular trafficking (movement) and targeting (direction) and, consequently, how transport vesicules containing newly-synthesized ion channels regulate transepithelial Cl secretion. To achieve these goals we study the polarized movement of the cAMP-activatable Cl channel, the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in differentiating epithelial cells. Utilizing modern physiological (patch-clamp), morphometric (real time confocal ratio-metric fluorescence) and molecular techniques, we are now in the process of identifying factors that facilitate the movement of CFTR-containing apical targeting vesicles. These studies offer the prospective student the opportunity to participate first hand, at the basic science level, in such fields as Cystic Fibrosis and Secretory Diarrhea.
Lastly, my laboratory is also involved in the study of intracellular second messengers, in particular the role of inositol polyphosphates in the modulation of [Ca2+]i and the activation of Ca2+-sensitive ion channels in epithelial cells. Three-dimensional computer modelling of [ion] with predefined time frames allows us to compartmentalize ion mediated signal transduction at the subcellular level. Again, these studies provide important insights into the control of fluid secretion under both normal and pathophysiological conditions.
