Larry Fliegel

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.