RESEARCH INTERESTS: Therapeutic intervention in diabetes via manipulation of carbohydrate metabolism enzymes and their genes

Short-term and long-term regulation of the enzymes of carbohydrate metabolism, namely, glucokinase, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, and glucose-6-phosphatase are the focus of the work in my laboratory. These enzymes are all regulated, either transcriptionally or by covalent modification, by the hormone insulin. The hormonal regulation and kinetic properties of these enzymes are studied by analysis of the promoters of their respective genes and structure/function analyses using site-directed mutagenesis of recombinant expressed forms of these enzymes.

We are specifically interested in the role these enzymes play in diabetes, both metabolically and as potential targets for gene therapy intervention. To test whether inhibition of the bisphosphatase domain of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase would provide therapeutic benefit to a diabetic patient, we are currently generating transgenic mice by gene targeting which are deficient in bisphosphatase activity.