The major thrust of my research lies at the crossroads of chemistry and biology. My group is currently working on three general areas with the focus aimed at the elucidation of the mechanisms of novel enzymatic reactions and the design of methods to control and/or regulate their functions.
Enzyme Mechanism and Inhibitor Design: Using a multi-faceted approach, we study the mechanisms of enzymes involved in diverse biological processes including the formation of bacterial cell wall, biosynthesis of and resistance to antibiotics, metabolism of lipids, and the posttranslational modification of nuclear proteins. A significant effort is devoted to the synthesis of compounds as mechanistic probes or specific inhibitors for these biological catalysts.
Metabolic Pathway Engineering: Through selective disruption and/or substitution of sugar biosynthetic genes in the microorganisms which produce bioactive glycosylated secondary metabolites, we have demonstrated the feasibility of engineering nature’s biosynthetic machinery for the production of novel compounds carrying designed sugar appendages. Such a combinatorial biosynthetic approach bears a great promise of finding drugs with new or improved biological activity.
Protein Function Regulation: We have recently initiated a study on poly(ADP-ribose) polymerase, an enzyme that recognizes damaged DNA and turns on the repairing machinery through polyADP-ribosylation of itself and other nuclear proteins. Such a posttranslational modification of proteins is also essential to other crucial cellular events including apoptosis.
Overall, most of the biological systems under investigation are target candidates for therapeutic drugs. My group is motivated by the challenge and excitement from understanding these biological transformations and tackling the relevant biomedical problems through chemical approaches.