In the present proposal we aim at investigating the role of de-ubiquitinating enzymes (DUBs) in Epithelial Ovaric Cancer (EOC) progression. In particular the focus of the project is to address the involvement of (DUBs) in DNA damage response and their contribution to tumor progression, focusing in particular on the acquisition of the chemoresistant and proangiogenic phenotypes. I will perform “loss-of-function” genetic screens through RNA interference using a commercial DUB shRNA library; I hope to identify specific DUBs that are implicated in the development of chemo-resistance and in the acquisition of the angiogenic phenotype. Finally, to determine the molecular mechanisms that underlie these tumorigenic phenotypes I will perform a mass spectrometric analysis to identify specific substrates targeted by DUBs.