Professor, Biochemistry and Biophysics
|
 |
| |
| Office: | ALS Bldg 2053 |
| Email: |  |
| Phone: | (541) 737-3119 |
| Links: |
Merrill Lab | | | Pub Med | | Keywords: | Thioredoxin; Cancer; P53; Tumor Suppressors; Oncogenes; Deoxyribonucleotide Metabolism; Saccharomyces cerevisiae; Oxidative Stress; Redox Regulation; Protein Thiols |
|
|
Education
Ph.D. 1977, Syracuse University
Research
Several important transcription factors and signal tranductionproteins are redox sensitive. These proteins often contain cysteine residues that are oxidized by reactive oxygen species and restored to the reduced state by thioredoxin. Thioredoxin is a redox active protein which, together with thioredoxin reductase, is able to transfer reducing equivalents from NADPH to oxidized protein cystinyl groups. Thioredoxin is required for proper functioning of several regulatory pathways. For example, the p53 tumor supressor protein requires reduced thioredoxin to efficiently stimulate target gene transcription. Similarly, protein tyrosine phosphatases, which antagonize the activity of tyrosine kinases, contain oxidation-prone cysteines that are maintained in a reduced state by thioredoxin. Our laboratory uses biochemical and genetic approaches to study the role of thioredoxin in redox control mechanisms. Biochemically, we have developed electrophoretic methods for measuring the redox state of proteins in vivo, and are using these methods to determine the basis for and consequences of oxidation events that occur during growth factor signaling and oxidative stress. Genetically, we use budding yeast, an organism where genes can easily be deleted or replaced, to study the effect of modifying redox control proteins on transcription factor activity and cell signaling. We are also using knock-out mice to test whether the functional relationships we have discovered in the yeast system hold true for mammalian cells.
