In this laboratory, we are studying 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 we study, these channels come in two "flavors"--the inositol 1,4,5 trisphosphate receptor (IP₃R) and the ryanodine receptor (RyR). We are interested in how these channels are regulated, inter-react and ultimately define the types of calcium signals we observe. To these ends, we use a variety of state of the art imaging and electrophysiological techniques, including high speed digital imaging, confocal microscopy and whole cell patch-clamp to monitor calcium signals with high spatial and temporal resolution. The hope is that a better understanding of the mechanisms which underlie these important signals will give insight into the control of important physiological processes in both normal physiology and disease states.

Oscillations of cytosolic calcium in a parotid acinus

Current projects in the lab are:

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.

3. Investigating defects in calcium signaling during acute pancreatitis.

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