Professor and Chair
Metalloenzymes; Protein Function and Structure
The major focus of my research program is to apply structural biology approaches to investigate structure-function relationships of proteins with significant medical relevance. We utilize a myriad of biophysical and biochemical technologies for our investigations. In general, X-ray crystallography is the main method used to elucidate the three-dimensional architecture of the protein. We then wed structure with function by carrying out functional and biophysical characterizations of the protein in conjunction with site-directed mutagenesis. Insights derived from these studies help us understand: how changes in protein sequence and structure are revealed at the biochemical, cellular, and organismal level; how drug compounds and small molecules modulate enzyme activity; and how the interplay between structure and function impacts fundamental biomedical processes that underlie healthy and diseased states.
A long-standing research interest within my laboratory has been on the characterization of enzymes that derivatize the acyl chains of lipid substrates. The resulting products play important structural roles in the stabilization and fluidity of biological membranes and serve as precursors in the production of bioactive lipids. Altered production of these lipid messengers results in the dysregulation of physiological processes that contribute to the pathogenesis of diabetes, obesity, leukodystrophies, inflammation, and many cancers. Current targets include the membrane-associated cyclooxygenase and fatty acid dioxygenase enzymes, as well as integral membrane fatty acid hydroxylase and desaturase enzymes.
We have also recently initiated collaborative studies to examine the structure-function relationships of novel virulence factors in Treponema denticola, one of the major virulent pathogens associated with chronic periodontitis. These pathogens have evolved complex mechanisms to evade host immune defenses, which allow them to thrive in the oral cavity. Our current focus is on the structural characterization of sialidase and cysteine protease enzymes.