(1984) U. of Saskatchewan, Saskatoon
(1990) U. of Saskatchewan, Saskatoon
Research Associate Professor of Pediatics
Office: 6029 Thurston-Bowles
Dr. Garbriel's research focuses primarily on molecular regulation of ion transport. The pulmonary airway surface is lined with a thin layer of liquid that is of primary importance in lung defense. It is well known that absorption and secretion of ions across the airway epithelium is responsible for maintaining the correct composition and volume of the airway surface liquid. What is not well known is i) the molecular identity of the channels and transporters responsible for this process, and ii) the mechanisms of regulation that coordinate the homeostasis of the pulmonary airway surface liquid.
It is generally accepted that airway epithelial cells are capable of both electrolyte absorption and secretion and that the net balance between these ion transport processes controls the movement of fluid by osmotic pressures. The ion channels lining the airway lumen constitute the rate-limiting step for both secretion and absorption. The basic route for Na+ absorption across the airway epithelium involves Na+ entry at the apical membrane via the Epithelial Na+ Channel (ENaC). Under conditions where Cl- secretion occurs (fetal liquid secretion) several Cl- channels are proposed to be involved including the cystic fibrosis transmembrane conductance regulator (CFTR; a cAMP-regulated Cl- channel), the calcium-activated Cl- channel (CaCC), and volume regulated Cl- channels (e.g., ClC family of channels). The Aquaporin family of water channels, which show a regional distribution of expression in the mammalian lung, mediate osmotically induced fluid secretion.
The long-term research interests of my research laboratory focuses on these ion and water channels and involves several ongoing projects. 1) Identification and molecular cloning of channels and regulators that affect airway surface liquid homeostasis. 2) Characterization of the long-term mechanism for regulation of Na+ absorption. 3) Understanding the role of CFTR as a regulator of other ion channels. 4) Determining the molecular interaction between ion channels and the mechanisms for coordinated regulation of channels. 5) Understanding the role of ion transport in disease pathogenesis, in particular cystic fibrosis.
The laboratory uses a variety of molecular biology and electrophysiological techniques to address questions concerning airway ion and fluid homeostasis. Molecular biology skills employed range from simple PCR amplifications, probe synthesis, northern blot analysis and in situ hybridization to more complex techniques including expression library construction and screening, differential display and subtractive hybridization. Several electrophysiological techniques are routinely employed to assess the function of candidate channels and regulators including, patch clamp (single channel and whole cell), transepithelial Ussing chamber voltage clamp protocols, and 2-electrode Xenopus oocyte voltage clamp protocols.
- S.E. Gabriel, S.E. Davenport, R.J. Steagall, V. Vimal, T. Carlson, and E.J. Rozhon, 1999. A novel plant-derived inhibitor of CFTR-mediated fluid and chloride secretion. American Journal of Physiology, 39:G58-G63.
- C.L. Talbot, D.G. Bosworth, E.L. Briley, D.A. Fenstermacher, R.C. Boucher, S.E. Gabriel, and P.M. Barker, 1999. Quantitation and localization of ENaC subunit expression in fetal, newborn and adult mouse lung. American Journal of Respiratory Cell and Molecular Biology, 20:398-406.
- S.E. Gabriel, E.J. Thomas, M. Belopolsky, S.P. Hardy, and M.I. Lethem. 2000. Expression of nucleotide regulated Cl- currents in immortalised CF and normal mouse tracheal epithelial cell lines. American Journal of Physiology, 279:C1578-1586.
- S.E. Gabriel, M. Belopolsky, E. Martsen, E.J. Thomas, M.I. Lethem, and R.C. Boucher. 2000. Permeablization via the P2X7 purinoreceptor reveals the presence of a Ca2+ –activated Cl- conductance in the apical membrane of CF and normal tracheal epithelial cells. Journal of Biological Chemistry, 275:35028-35033.
- S. Kreda, M Gynn, D.A. Fenstermacher, R.C. Boucher, and S.E. Gabriel. 2001. Expression and localization of epithelial aquaporins in human adult respiratory tissue. American Journal of Respiratory Cell and Molecular Biology. In Press.
- S.H. Donaldson, A. Hirsh, D.C. Li, G.L. Holloway, JM. Chao, RC. Boucher, and S.E. Gabriel. 2001. Regulation of the Epithelial Sodium channel by Serine Proteases in Airways. American Journal of Physiology,Submitted.