Our laboratory focuses on understanding mechanisms of diseases associated to the digestive system, with a special focus on liver and intestinal diseases. By employing multi- and inter-disciplinary approaches, including the use of mouse models mimicking human disease combined with human data, we aim to: find out what goes wrong in diseased and cancerous tissues; understand how organs can regenerate; potentially engineer new tissues; and, if regeneration goes awry, determine how it contributes to cancer.
Our interest is mainly driven by the discovery of two components initially identified in our laboratory to be downstream targets of the growth factor and nutrient signalling cascades: the URI (Unconventional prefoldin RPB5 Interactor) and MCRS1 (Microspherule protein 1) proteins. URI and MCRS1 expression turned out to be regulated in response to various environmental factors (radiation, nutrients, bacteria, viruses, etc.), compromising their functions and activating pleiotropic circuits to support complex cell signalling networks, provoking severe outcomes. Importantly, URI and MCRS1 are respectively part of 2 independent protein complexes: the URI prefoldin-like and the non-specific lethal (NSL) complexes. While URI might have some co-chaperone activities to maintain proteostasis, we identified MCRS1 to be a new regulator of histone acetylation and, therefore, a central component of the chromatin modifier complex NSL, whose loss in hepatocytes leads to cirrhosis development.