Oliver, Javier

Involvement of PARP in the regulation of tumor response to hypoxia. Identification of key PARylated proteins during hypoxia and mechanistic elucidation of their implication in the global reprogramming of tumor cells during hypoxia.

Regulation by PARP-1 of the autophagy and implication in the adaptation to the tumor microenvironment. Autophagy is a highly regulated cellular process that serves to remove damaged proteins and organelles in the cell. The role of autophagy in cancer is complex and probably dependent on tumor type, staging and genetic context. This complexity is illustrated by the identification of situations in which autophagy acts both as a potent promoter and as inhibitor of tumorogenesis. The foundation of these opposing functions is not yet understood. Results from our laboratory have shown that the presence and / or activation of PARP-1 plays an active role in the induction of autophagy and its inhibition directs cell death towards apoptosis during the autophagy process . In this line of work, we focus on the interaction mechanism of PARP-1/PARylation with the autophagy machinery and the consequences of hypoxia-induced inhibition of autophagy on the progression towards the acquisition of the malignant phenotype in different tumor settings (melanoma, glioblastoma and breast cancer) as well as its regulation by PARP inhibitors.