I completed my doctorate in Molecular Pharmacology at the University of Pittsburgh in 2000. I then received post-doctoral training in biophysics at Vanderbilt University. During this time, I became interested in developing fluorescent imaging methods to study the regulation of insulin secretion. I joined the Department of Physiology in 2005.

Our primary research focus is on understanding the molecular mechanisms that regulate insulin secretion from pancreatic beta cells. Insulin release is primarily regulated by rises in blood glucose. The concentration of glucose is sensed by glucokinase, and the sensitivity of this reaction can be modulated by a number of cell surface receptors, including members of the G-protein coupled receptor family. We use a variety of biochemical, quantitative imaging, and structural methods to understand the molecular and cellular mechanisms of glucokinase regulation.

Active projects in the lab include:

• Structural effects of glucokinase nitrosylation. Reaction of a single cysteine in glucokinase with nitric oxide activates glucokinase. We are using molecular dynamics simulations and fluorescence spectroscopy to understand the functional consequences of the conformational changes produced by this reaction.

• Cellular regulation of nitric oxide synthase activation by release of calcium from intracellular stores. Nitric oxide synthase is an important regulator of gluockinase nitrosylation, and its activity is controlled by rises in intracellular calcium. Calcium handling is tightly regulated in the β cell, and we are investigating the regulation of intracellular calcium release by G-protein coupled receptors using genetically encoded calcium sensors and high-speed fluorescence imaging.

• Construction of novel fluorescent protein biosensors. Often, the available fluorescent probes have insufficient fluorescence and spectral properties to accommodate the measurements we require. To meet our needs, we bioengineer
novel fluorescent protein variants using structure-based design and semi-rational
site directed mutagenesis techniques. 

                                                                                                                                           Above: This rendering shows simulated 
                                                                                                                                                       structures of nitrosylated (green)
                                                                                                                                                       and native (blue) glucokinase.

My laboratory uses biochemical and spectroscopic techniques in addition to quantitative, live cell fluorescence microscopy methods, such as FRET and FRAP. We also utilize molecular dynamics simulations in conjunction with molecular biology techniques to bioengineer novel fluorescent proteins.