Venue: Edificio Povo 2, via Sommarive nr. 9, Povo (TN) - Room B101
at 1:30 p.m.
- Joaquín M. Espinosa, Howard Hughes Medical Institute and University of Colorado at Boulder
p53 is the most commonly inactivated tumor suppressor gene in human cancer. The p53 gene network is composed of functionally distinct gene modules mediating diverse cellular responses to stress including cell cycle arrest, senescence, apoptosis and autophagy. The molecular mechanisms defining how cells adopt a specific response upon p53 activation are poorly understood, which hampers the development of therapies harnessing the apoptotic potential of p53 for selective elimination of cancer cells. Why do some cell types survive whereas others die upon p53 activation? Several projects in our lab investigate how pleiotropy is generated within the p53 transcriptional program and how the network can be manipulated to produce specific cellular responses upon p53 activation. We performed mechanistic studies using global measurements of nascent RNA synthesis (GRO-seq), steady state RNA levels (microarray gene profiling) and p53 occupancy (ChIP-seq) to demonstrate how the p53 transcriptional program is qualified at the transcriptional and post-transcriptional levels. We have also performed genome wide shRNA screens to identify signaling pathways that control the cellular response to p53 activation. Finally, we employed this knowledge to improve the therapeutic efficacy of p53-based targeted therapies currently being tested in clinical trials for the treatment of various cancers