In a broad sense, my laboratory focuses on understanding the underlying mechanisms whereby cancers demonstrate resistance to radiation and chemotherapy and characterizing normal cell/tissue responses to radiation therapy. This information will give us a framework to develop ways to target oncogenic pathways that lead to therapeutic resistance and identify potential molecular interventions that may reduce the normal tissue complications of radiation therapy. One major focus concerns the elucidation of mechanisms whereby the tumor suppressor p53 regulates transcriptional repression and more specifically how these pathways influence response to radiation. Recently, we have identified two transcriptional co-repressors which appear to be p53-regulated targets. We hypothesize that the loss of this putative repression mechanism in the context of neoplastic conversion may contribute to tumor progression and/or therapeutic resistance. A second area of interest is the application of in vivo imaging methods to preclinical studies in relevant biological models of cancer with a focus on high-grade brain tumor biology. This includes evaluation of the efficacy of novel therapeutic combinations in preclinical animal models and determination of timing, dosage, and in vivo mechanisms of anti-tumor action.