Paula Bartlett, PhD

My research interrogates the mechanisms which elicit and maintain hormone-induced Ca2+ oscillations in primary hepatocytes. In liver hepatocytes hormonal regulation of Ca2+ signaling underlies many of the primary functions of the organ including glucose metabolism, mitochondrial physiology and gene expression. Hormones which couple to phospholipase C (PLC), Gq-linked G-protein coupled receptors (GPCRs), hydrolysis the membrane phosphoinositide lipid PIP2 to generate inositol 1,4,5-trisphosphate (IP3), and diacylglycerol (DAG), which in turn regulate cell function via Ca2+ release and PKC activation. Hepatocytes display stimulus-strength regulated Ca2+ oscillations and waves importantly the pattern of intracellular Ca2+ fluctuations encodes complex spatial and temporal information to regulate cell function. We utilize single cell digital fluorescent imaging techniques combined with biochemical techniques to dissect the mechanisms which generate, maintain and regulate Ca2+ oscillations. These studies address the ongoing debate, whether Ca2+ oscillations arise due to Ca2+ feedback on the IP3 receptor or as a consequence of fluctuations in IP3, hence phospholipase C activity. Our studies have provided compelling evidence that Ca2+ oscillations in hepatocytes depend on IP3 fluctuations arising from positive Ca2+ feedback on PLC.