Larry Fliegel
Professor
Ph.D, University of Calgary
Office: 780-492-1848
Lab: 780-492-1847
Fax: 780-492-0886
lfliegel@ualberta.ca
Research:
Handling acid is a problem in all organisms. As a result of metabolism, excess intracellular acid is produced in all cells. Too much acid has a deleterious effect on the activity of various enzymes and results in abnormalities in metabolism and cell cycle. In the heart, too much acid inhibits contractile activity and damages the myocardium. Our laboratory studies the regulation of intracellular pH and the removal of excess intracellular acid. In mammalian tissues the main protein responsible for this is the Na+/H+ exchanger. The Na+/H+ exchanger is a mammalian plasma membrane protein that exchanges one intracellular proton for an extracellular sodium. It is involved in pH regulation and is stimulated by growth factors. Several isoforms of the protein exist (NHE1 to NHE10). NHE1 is the most widespread and exists in all mammalian cells. My laboratory has studied many aspects of the NHE1 protein. We have examined the structure and characterized activity of the protein. We have used site-specific mutagenesis to discover which amino acids are important in transport and have examined the structure of parts of the cytosolic and membrane domains. In collaboration with others we have elucidated the structure of parts of the membrane domain of the protein. My laboratory has also studied phosphorylation of the antiporter and factors affecting localization and targeting of the protein.
Selected Publications:
The Na+/H+ exchanger (NHE1) as a novel co-adjuvant target in paclitaxel therapy of triple-negative breast cancer cells.
Amith SR, Wilkinson JM, Baksh S, Fliegel L.
Oncotarget (2015) 6(2):1262-75.
Mutation of SLC9A1, encoding the major Na+/H+ exchanger, causes ataxia-deafness Lichtenstein Knorr syndrome.
Guissart C, Li X, Leheup B, Drouot N, Montaut-Verient B, Raffo E, Jonveaux P, Roux AF, Claustres M, Fliegel L, Koenig M.
Hum Mol Genet. (2015) Jan 15;24(2):463-70.
Structural and functional analysis of the transmembrane segment Pair VI and VII of the NHE1 isoform of the Na+/H+ Exchanger.
Alves C, Lee BL, Sykes BD, Fliegel L.
Biochemistry (2014) 53(22):3658-3670.
Structural and functional analysis of transmembrane segment IV of the salt tolerance protein sod2.
Ullah A, Kemp G, Lee B, Alves C, Young H, Sykes BD, Fliegel L.
J. Biol Chem. (2013) 288:24609-24624.
B-Raf associates with and activates the NHE1 isoform of the Na+/H+ exchanger.
Karki P, Li X, Schrama D, Fliegel L.
J. Biol. Chem. (2011) 286(15):13096-13105.
Activated NHE1 is required to induce early cardiac hypertrophy in mice.
Mraiche F, Oka T, Gan XT, Karmazyn M, Fliegel L.
Basic Research Cardiology (2011)106:603-616.
Structural and functional analysis of TM XI of the NHE1 isoform of the Na+/H+exchanger.
Lee BL, Li X, Liu Y, Sykes BD, Fliegel L.
J. Biol. Chem. (2009) 284:11546-11556.
Lab Members
Research Associate
Xiu Ju Li
Links
Location
Office: 345a MSB
Lab: 345 MSB