It is estimated that up to 20% of Americans suffer from xerostomia, (dry mouth). Multiple factors are associated with this disease, including defects in the genes that encode for water and ion transport proteins.
The focus of my laboratory is to determine the molecular identity of the transport proteins that regulate fluid secretion. We are using an interdisciplinary approach to provide information about the structure and the physiological roles of these transport proteins. Insight gained from these studies will provide critical information for developing rationales for preventing and/or treating exocrine gland dysfunction.
Specifically, we have four major NIH-funded projects:
- Salivary gland secretory cells express at least five distinct chloride channels including cAMP-activated, hyperpolarization-dependent, ATP-activated, volume-sensitive, and calcium-dependent channels. The former 2 channels are encoded by the Cftr and Clcn2 genes, respectively; whereas, the molecular identities of the latter 3 channels are unknown. Molecular biology, gene knockout, and electrophysiological technologies are being used to characterize these channel proteins;
- Multiple sodium/proton exchangers (NHE1-4) are expressed in salivary gland cells. These exchangers regulate acinar cell fluid secretion and NaCl reabsorption in the ducts. We are characterizing clones of these proteins to examine structure-function relations, and are determining the functional consequences of gene ablation in mice;
- The role of the AQP5 water channel (aquaporin 5) in salivary secretion is being investigated using a combination of cell biology, physiological and genomic approaches to analyze a mouse in which Aqp5 has been ablated by gene targeting; and
- The functional consequence of potassium channel gene disruption on salivary gland function is being assessed.
A second component of this study is to characterize the ion transport proteins expressed in human salivary gland acinar cells. The results of these studies will be correlated with findings from studies of humans suffering from dry mouth disease in an attempt to develop new treatments for these individuals. |
