Medicine & Dentistry-Biochemistry
University of Alberta
Summary of research:
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 the 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. My laboratory studies many aspects of the 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. The NHE1 protein is also involved in breast cancer. 'Hyperactivation' of the protein acidifies the extracellular environment, promoting cell metastasis. We are presently deducing the aberrant mechanisms involved.