Sirtuin Discovery

The response to genotoxic or metabolic stress conditions has a major impact on the maintenance of genome integrity and is intimately linked to the development of many human pathologies and aging. The onset and development of different types of cancers, such as haematological malignancies, are strongly influenced by this response which makes it a promising therapeutical approach. The members of the sirtuin family of NAD⁺ - dependent enzymes are key coordinators of this response as they play an important role in the crosstalk between environment and the genome, at both a cellular and a physiological level. Particularly, they have a crucial role in the maintenance of genome stability, epigenetics, metabolic homeostasis, cell differentiation and development. Our main goal is to define the epigenetic mechanisms ruling this sirtuin-dependent response and their functional implications in genome stability, cancer, and aging. For that purpose, we employ a multidisciplinary approach that ranges from in vitro studies to in vivo mouse models and combines Biochemistry, Genetics and Molecular and Cellular Biology.