This laboratory has focused on understanding mechanisms of programmed cell death occurring in the nervous system after injury, in oncogenesis and in neurodegenerative disorders. The p53 protein is a site specific transactivator or repressor of transcription that promotes injury-induced programmed cell death by modulating the expression of select target genes. Defects in the p53 signaling pathway have been identified in nearly half of all human cancers, including many central nervous system malignancies. Studies have also implicated p53 in the pathogenesis of neuronal cell death occurring after DNA damage or ischemia, or in neurodegenerative diseases such as Huntington痴 Disease and Alzheimer痴 Disease. Moreover, the effects of many of the current clinical therapies for brain tumors (including radiation and some forms of chemotherapy) require activation of p53-dependent pathways. The cellular consequences of p53 activation in the nervous system are poorly understood, and a comprehensive study of p53-dependent changes in gene and protein expression in neurons, glia and brain tumor cells is needed. Our research combines mRNA microarray and mass spectrometry proteomics with other cell and molecular biology techniques to examine cell death pathways activated by various forms of injury in mouse neurons or glia, or in primary human glioma cells. Once identified, proteins essential to injury-mediated programmed cell death are investigated further to elucidate their function. A better understanding of these cell death mechanisms may lead to the development of more effective therapies for the treatment of brain tumors or nervous system injury.