Research Interests

Efficient intracellular electron transfer is essential to organisms that use oxygen. An exquisite balance between oxidized and reduced enzymes and cofactors, termed redox homeostasis, must be carefully regulated to maintain cellular function. Loss of redox balance underlies molecular changes associated with aging and age related diseases. Consequences of acute or chronic disruption in redox homeostasis include neurodegenerative diseases, cancer, diabetes mellitus, atherosclerosis, and rheumatoid arthritis.

In our lab, we are studying the enzymes that control the levels of thioredoxin (Trx) and glutathione (GSH), the major thiol based redox buffer systems. These parallel yet distinct systems are essential in cellular processes such as detoxification of reactive oxygen and nitrogen species, nucleotide biosynthesis, modulation of protein function, and cellular signaling of apoptosis and differentiation. Despite intensive research in these areas, critical molecular details are lacking that would facilitate the design of more effective treatments capable of modulating the intracellular redox state.

In collaboration with Dr. Melanie Simpson, we are also studying enzymes involved in hyaluronan production. Hyaluronan, a polymer comprised of a repeating disaccharide, has been shown to be important in prostate cancer progression, wound healing, normal heart development and other critical developmental processes. However, relatively limited structural and mechanistic information is available for the enzymes responsible for its biosynthesis and degradation. Specifically, we are working on UDP-glucose dehydrogenase (UGDH), which provides an essential precursor for hyaluronan production, and hyaluronidase (Hyal), which processes hyaluronan into smaller pieces with specific biological functions.