Prof ANTONIO SIMEONE Direttore
Phone number: +39 081 6132 403
Most of our research activity is centred on the transcription factor TBX1, whose haploinsufficiency causes most of the clinical findings associated with DiGeorge syndrome. We use mouse models to dissect the function of the gene encoding Tbx1 in various organs, especially the heart. In the human disease, the genetic defect is a reduction in dosage of TBX1 rather than a complete loss of function of the gene. Therefore, we are particularly interested in establishing the transcriptional changes that are associated with dosage reduction of this gene. The main role of Tbx1 in cardiovascular development is maintaining cell proliferation and preventing differentiation of a population of multi-potent heart progenitor cells. We are exploring the mechanisms by which Tbx1 carries out these functions. In particular, we are determining how Tbx1 functions to maintain or induce cell cycle re-entry and how it acts as a repressor of the cardiac differentiation transcription programme. We are considering interactions of Tbx1 with major signalling systems such as FGF, BMP and WNT. Given these important functions of Tbx1 in cardiac progenitors, we are using the gene as an entry point to identify genetic networks that control cardiac stem cell homeostasis. The goal of this particular project is to devise molecular and pharmacological methods to achieve controlled proliferation and differentiation of cardiac stem cells for heart repair.