Dr. Bezprozvanny's research at UT Southwestern focuses on the functional properties and modulation of intracellular Ca2+ release channels and voltage-gated Ca2+ channels. His laboratory developed a major project on structure-function analysis of the inositol trisphosphate receptor (InsP3R). Although the InsP3R had been cloned ten years previously, no one had successfully expressed a functional channel protein. Dr. Bezprozvanny's laboratory was the first to obtain functional recordings of recombinant InsP3R activity in bilayers. His laboratory is taking an advantage of this approach to analyse InsP3R structure-function. While developing this research, he achieved significant conceptual advances in the field of Ca2+ signaling. Most notably, he proposed a novel InsP3R-PIP2 signaling model of Ca2+ wave initiation and identified key determinants of InsP3R1 modulation by Ca2+ and phosphorylation. He also launched another research program on the mechanisms of targeting and localization of voltage-gated Ca2+ channels in neurons. Dr. Bezprozvanny was the first to discover a potential targeting motif required for synaptic targeting of neuronal voltage-gated Ca2+ channels. These results provide novel insights into synaptic function. The long-term goal of his lab is to characterize the functional differences between multiple InsP3R isoforms and to determine structural determinants responsible for their major functional properties.
