Our research focuses on basic posttranscriptional mechanisms that control protein abundance and function. We concentrate on conserved pathways regulating protein synthesis at the level of translation and protein degradation through the ubiquitin-proteasome system. For many of these studies, we are using the fission yeast Schizosacharomyces pombe as a model system. Our studies also employ a variety of genome-wide approaches such as proteomics and ribonomics. Our goals are (1.) to define translation initiation complexes that mediate stress-specific mRNA translation; (2.) to define and characterize novel substrates of cullin-RING ubiquitin ligases, and (3.) to integrate large scale mRNA and protein expression datasets into a systems view of oxidative stress response. We are also applying insights derived from our studies in fission yeast to the biology of human cancer. In particular, we are seeking ubiquitin ligases targeting several tumor suppressor proteins involved in prostate cancer. We are also performing high-throughput screens for small molecule inhibitors of ectopic degradation of prostate tumor suppressors.