Overview

Cellular processes ranging from fertilization to programmed cell death are regulated by precisely timed changes in the intracellular free calcium (Ca²⁺) concentration. Cells therefore are equipped with mechanisms to tightly control the influx, efflux and resting level of Ca²⁺. Inappropriate Ca²⁺ signaling and disturbed Ca²⁺ levels are involved in a multitude of clinical disorders including heart disease, Alzheimer’s disease and stroke. Ca²⁺ also plays a major role in cell growth, differentiation and motility; disturbances in these processes underlie cell transformation and the progression of cancer. Our laboratory is interested in the mechanisms of localized Ca²⁺ signaling and in the molecular “toolkit” needed to ensure proper Ca²⁺ homeostasis in the cell. Of particular interest are the structure, regulation, cellular targeting and physiological function of plasma membrane Ca²⁺ pumps. These pumps are the major high-affinity calcium extrusion system of all cells and are particularly abundant in epithelial cells and neurons where they play important roles in Ca²⁺ transport across cell layers and in signal transmission, respectively. We also study the function and mechanism of action of an epithelial-specific calmodulin-like “Ca²⁺ sensor” protein that is down-regulated in breast cancer and other epithelial cancers. Current results suggest that this protein is a Ca²⁺-sensing component of a novel myosin and may function in cell motility during terminal epithelial differentiation. Our laboratory uses a variety of biochemical, cellular and molecular techniques including spectroscopy for equilibrium and kinetic measurements, yeast two-hybrid screens, expression of epitope-tagged proteins, and confocal fluorescence microscopy.