The primary area of research in my laboratory is concerned with the structure, mechanism and physiological role of the aldo-keto reductase enzymes, specifically aldehyde and aldose reductase and recently isolated homologues. These enzymes catalyze the reduction of a broad variety of aldehydes and they are structurally very similar. However, they exhibit differences in both substrate and coenzyme specificity and one objective of our research is to determine the reason for these differences. The crystallographic structures of aldehyde and aldose reductase are known as well as the aldose reductase homolgues FR-1 and CHO reductase. Our current research is focussed on the structural differences that allow subtle but distinct substrate specificities and on refining the catalytic mechanism through site-directed mutagenesis of active site residues. In addition we are currently assessing the regulation of expression of aldose reductase and related enzymes which have been shown to be under either osmotic or hormonal control. A new and exciting area of research also is the potential role of the aldo-keto reductases in carcinogenesis both as a biomarker and through their ability to detoxify some commonly used anticancer drugs.