The work in Dr. DeFranco's laboratory is divided between three separate projects. One group in the laboratory studies steroid receptor function and focuses on their subcellular trafficking, degradation, and transcriptional regulatory properties. The work on glucocorticoid receptors utilizes various cell culture models including primary hippocampal neurons, while androgen receptor function is studied in prostate cancer cell lines. Another group in the laboratory studies the role of various signaling cascades, particularly the mitogen-activated protein kinase (MAPK) pathway, in neuronal cell death. Immature rat embryonic cortical neurons, as well as hippocampal cell lines are currently used as models with a primary focus on mechanisms of oxidative toxicity. In addition, MAPK signaling is being examined in a rat model of global ischemia (i.e. asphyxia-induced cardiac arrest). One other project in the DeFranco laboratory focuses on the mechanism of toxicity induced by the gene (i.e. huntingtin) responsible for Huntington’s Disease (HD). In this study, various molecular, biochemical and cell biological approaches are utilized to examine the impact of mutant huntingtin expression on transcription factor function and protein degradation. These studies primarily utilize neuronal cell lines and primary neurons with some validation work in a transgenic mouse model of HD.