The Yule laboratory studies intracellular calcium signaling in cells which are typically, electrically non-excitable. In cells such as the liver, exocrine, pancreas, salivary glands and various cells in the blood, increases in intracellular calcium are fundamentally important for diverse processes including secretion of digestive enzymes and fluid, glucose metabolism together with cellular growth and differentiation. An important event in triggering an elevation in intracellular calcium is the activation of intracellular Ca2+ release channels in the endoplasmic reticulum. In most cells the lab studies, these channels come in two "flavors"--the inositol 1,4,5 trisphosphate receptor (IP3R) and the ryanodine receptor (RyR). Current projects include: 1. Determining the mechanisms whereby different agonists using traditionally the same intracellular messengers can generate agonist specific calcium signals and activate specific cellular processes, 2. Investigating if a genetic defect in the calcium signaling machinery expressed in salivary gland cells is responsible for patients with some forms of "dry mouth' disease, and 3. Investigating structure function relationships of inositol 1,4,5-trisphosphate receptors.