Our studies explore the molecular nature of the secretion process and the (patho)physiological properties of cells in the exocrine salivary gland with the ultimate goal to use the insight gained to treat salivary gland hypofunction. Specifically, the Secretory Mechanisms and Dysfunction Section investigates the molecular nature and function of the ion transport mechanisms involved in the fluid and electrolyte secretion process in the exocrine salivary gland by probing the structure-function relationships of cotransporter, exchanger and channel proteins using a combination of molecular biology, gene modification, proteomics and functional studies in mouse and human salivary glands. High-throughput approaches are used to catalogue the human saliva and salivary gland proteomes, to identify salivary biomarkers for human diseases, and to compile a comprehensive list of the plasma membrane proteins expressed in salivary glands. This information is critical to the development of specific and effective interventions to treat xerostomia (dry mouth) that minimize side effects. Ultimately, we plan to test the clinical effectiveness of secretion activators in different subject populations available for study at the NIH.