DVM Program Courses:
Associate Membership in Other Departments:
This research program is aimed at developing an in-depth knowledge of the movement of chloride across cells lining the airway. Proteins called channels allow the movement of chloride out of cells and onto the airway surface. The chloride pulls water with it, thus properly hydrating the airway and protecting it against infection.
The program's long-term goal is to discover and define the contribution of channels and related proteins involved in chloride movement in both normal and diseased airway cells. Two short term objectives will be addressed over the next five years regarding the role and action of one specific protein that modulates chloride channels.
Initially, the specific gene of the channel that the modulating protein acts upon will be identified. Secondly, how the specific protein interacts within the identified channel's structure will be determined, thereby defining a mechanism for a phenomenon that has eluded explanation for over 15 years.
Graduate students involved in this research and will receive extensive training in molecular, biochemical, and electrophysiology techniques, skills which are highly desirable and sought after by pharmaceutical industry employers.
Finally, the knowledge gained through this research will lead to a better understanding of respiratory diseases that impact Canadians, such as cystic fibrosis, asthma, and chronic obstructive pulmonary disease (COPD), and will lead to the development of innovative treatments.
In collaboration with members of the Vaccine and Infectious Disease Organization (VIDO) and the WCVM's Department of Small Animal Clinical Sciences, we are beginning to probe the mechanism of block of novel compounds to wild type and drug resistant mutations of the M2 proton-selective ion channel of the influenza A. In-silico modeling, ITC and electrophysiological techniques will be used to understand the block of novel compounds.
Eldstrom J, Xu H, Werry D, Kang C, Loewen ME, Degenhardt A, Sanatani S, Tibbits GF, Sanders C, Fedida D. 2010. "Mechanistic basis for LQT1 caused by S3 mutations in the KCNQ1 subunit of IKs." Journal of General Physiology. 135: 433-48.
Loewen ME, Wang Z, Eldstrom J, Zadeh AD, Khurana A, Steele D, Fedida D. 2009. "Shared requirement for dynein function and intact microtubule cytoskeleton for normal surface expression of cardiac potassium channels." American Journal of Physiology — Heart and Circulatory Physiology. 296: H71-83.
Zadeh AD, Xu H, Loewen ME, Noble GP, Steele DF, Fedida D. 2008. "Internalized Kv1.5 traffics via Rab-dependent pathways." The Journal of Physiology. 586: 4793-813.
Chappe F, Loewen ME, Hanrahan JW, Chappe V. 2008. "Vasoactive intestinal peptide increases cystic fibrosis transmembrane conductance regulator levels in the apical membrane of Calu-3 cells through a protein kinase C-dependent mechanism." The Journal of Pharmacology and Experimental Therapeutics. 327: 226-38.
Steele DF, Loewen ME*, Zadeh AD*, Fedida D. 2007. "Localization and trafficking of cardiac voltage-gated potassium channels." Biochemical Society Transactions. 35: 1069-73. (*) Equal Contribution.
Appleyard GD, Forsyth GW, Kiehlbauch LM, Sigfrid KN, Hanik HLJ, Quon A, Loewen ME, Grahn BH. 2006. "Differential mitochondrial DNA and gene expression in inherited retinal dysplasia in miniature Schnauzer dogs." Investigative Ophthalmology Visual Sciences. 47: 1810-6.
Bekar LK, Loewen ME, Forsyth GW, Walz W. 2005. "Chloride concentration affects Kv channel voltage-gating kinetics: Importance of experimental anion concentrations." Brain Research Buletin. 67: 142-6.
Loewen ME, Forsyth GW. 2005. "Structure and function of CLCA proteins." Physiological Reviews. 85: 1061-92.
Bekar LK, Loewen ME, Cao K, Sun X, Leis J, Wang R, Forsyth GW, Walz W. 2005. "Complex expression and localization of inactivating Kv channels in cultured hippocampal astrocytes." Journal Neurophysiology. 93: 1699-709.
Hammond GM, Loewen ME, Blakley BB. 2004. "Diagnosis and treatment of zinc poisoning in a dog." Veterinary and Human Toxicology. 46: 272-5.
Hanik HL, Loewen ME, Appleyard GD, Grahn BH, Forsyth GW. 2004. "Differences in expression of retinal pigment epithelium mRNA between normal canines." Canadian Journal of Veterinary Research. 68: 201-7.
Loewen ME, Bekar LK, Walz W, Forsyth GW, Gabriel SE. 2004. "pCLCA1 lacks inherent chloride channel activity in an epithelial colon carcinoma cell line." American Journal of Physiology - Gastrointestinal and Liver Physiology. 287: G33-41.
Loewen ME, Smith NK, Hamilton DL, Grahn BH, Forsyth GW. 2003. "CLCA protein and chloride transport in canine retinal pigment epithelium." American Journal Physiology - Cell Physiology. 85: C1314-21.
Loewen ME, Bekar LK, Walz W, Forsyth GW, Gabriel SE. 2004. "pCLCA1 lacks inherent chloride channgel activity in an epithelial colon carcinoma cell line." American Journal of Physiology - Gastrointestinal and Liver Physiology. 287: 33-41.
Tarran R, Loewen ME, Paradiso AM, Olsen JC, Gray MA, Argent BE, Boucher RC, Gabriel SE. 2002. "Regulation of murine airway surface liquid volume by CFTR and Ca2+-activated Cl-conductances." Journal of General Physiology. 120: 407-418.
Loewen ME, Gabriel SE, Forsyth GW. 2002. "The calcium-dependent chloride conductance mediator pCLCA1." American Journal of Physiology — Cell Physiology. 283: 412-421.
Gaspar KJ, Racette JK, Gordon JR, Loewen ME, Forsyth GW. 2000. "Cloning of a chloride conductance mediator from the apical membrane of porcine ileal enterocytes." Physiological Genomics. 3: 101-111.
Loewen ME, MacDonald DW, Gaspar KJ, Forsyth GW. 2000. "Isoform-specific exon skipping in a variant form of ClC-2." Biochimica Biophysica Acta 1493: 284-288.