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Paul Luther McNeil, Ph.D.
E-mail:
Research Emphasis:
The laboratory's long-term goal is to understand the subcellular and molecular basis of the cell's response to a temporary disruption in plasma membrane integrity, an event which is commonly induced in many tissues in vivo by physiological levels of mechanical stress. Questions presently under investigation include the following. Is the early endosomal compartment mobilized to sites of plasma membrane disruption? What is the identity of the molecules that participate in the disruption-induced vesicle mobilization and exocytotic response, now known to mediate resealing of disruptions? What is the molecular basis for the tolerance for mechanical stress that cells develop after suffering a plasma membrane disruption? Is gene expression induced by membrane disruption, and, if so, what is the identity of the genes/ protein products? What is the molecular explanation for the differential sensitivity to mechanical stress displayed by mammalian cells of different tissues of origin? A wide variety of techniques are used in the laboratory including, flow
cytofluorometry, Western blotting, cell culture, computer-aided image analysis of immunostained tissue, Northern blotting, cloning, and
PCR.
Selected Publications:
McNeil PL, Khakee R (1992) Disruptions of muscle fiber plasma membranes: role in exercise-induced damage. Amer J Pathol 140:1097-1109.
Clarke MSF, McNeil PL (1992) Syringe loading introduces macromolecules into living mammalian cell cytosol. J Cell Sci 102:533-541.
Yu QC, McNeil PL (1992) Transient disruptions of the plasma membranes of endothelial cells of the rat aorta. Amer J Pathol 141:1349-1360.
Paimela H, Goddard PJ, Carter K, Khakee R, McNeil PL, Ito S, Silen W (1993) Restitution of frog gastric mucosa in vitro: effect of bFGF. Gastroentrol. 104:1337-1345.
Clarke MSF, Khakee R, McNeil PL (1993) A mechanism for the release of basic fibroblast growth factor from normal and dystrophic muscle. J Cell Sci 106:121-133.
Clarke, M.S. F., C. R. Vanderburg, E. D. Hay and P. L. McNeil (1994) Cytoplasmic loading of dyes, protein and plasmid DNA using an impact mediated procedure. Biotechniques. 17: 1118-1125.
Clarke, M. S. F., R. W. Caldwell, H. Chiao, K. Miyake and P. L. McNeil (1995) Contraction-induced cell wounding and release of fibroblast growth factor in the rat heart. Circ. Res. 76:927-934.
Miyake, K. and P. L. McNeil (1995). Vesicle accumulation and exocytosis at sites of plasma membrane disruption. J. Cell Biol. 131: 1737-1745.
Clarke, M. S. F., K. A. Pritchard, M. S. Medow and P. L. McNeil (1996) An atherogenic level of native LDL increases endothelial cell vulnerability to shear stress-induced plasma membrane wounding and consequent release of basic fibroblast growth factor. Endothelium (in press).
Kaye, D., D. Pimental, S. Prasad, T. Moki, H.-J. Berger, P.L. McNeil, R. Kelly and T.W. Smith (1996). Role of transiently altered sarcolemmal membrane permeability and bFGF release in the hypertrophic response of adult rat ventricular myocytes to increased mechanical activity in vitro. J. Clin. Invest. (in press).