Ph.D. 1977, Syracuse University
The thioredoxin system, consisting of the small redox-active protein thioredoxin and the large selenocysteine-containing enzyme thioredoxin reductase, has been implicated in several enzymatic and regulatory processes. For example: it can provide electrons for the enzymatic reduction of ribonucleotides, peroxides and sulfoxides; it can support target gene binding and activation by p53, NFkB and AP1; and it can restore oxidatively inactivated protein tyrosine phosphatases to the reduced and active state. Our laboratory uses genetic and biochemical approaches to study the biological roles of thioredoxin. Genetically, we use budding yeast and knockout mice to study the effects of deleting thioredoxin reductase on cancer rates, metabolism, transcription factor activity and cell signaling. Biochemically, we have developed methods for measuring the redox state of proteins and small molecules in vivo, and are using these methods to determine the real consequences of thioredoxin reductase ablation. Our results suggest thioredoxin reductase plays a physiological role in reducing protein disulfides, suppressing inflammation, and maintaining carbonyl homeostasis.