THE ROLE OF GLUCOCORTICOID RECEPTOR AND STAT3 IN THE REGULATION OF MITOCHONDRIAL METABOLISM

My research activity has focused on the study of two fundamental transcription factors: the Signal Transducer and Activator of Transcription 3 protein (STAT3) and the Glucocorticoid Receptor protein (GR). I focused my attention on the non-canonical functions of these important proteins, investigating both their nuclear activities and their less characterized mitochondrial functions. Finally, I have also analysed their possible functional cross talk in the regulation of gene transcription. More in detail, I started my PhD course studying STAT3 protein functions and the role of its post-translational modifications (reviewed in Tesoriere et al., 2021). The research activity of our group is focused on the use of zebrafish as model organism to study in vivo the non-canonical mechanisms of Stat3, for example the Stat3 mitochondrial functions and the Stat3 activities related to the crosstalk with other proteins. During my PhD I participated in the characterization of Stat3 mitochondrial functions (Peron et al., 2021), contributing to the obtaining of a new zebrafish mutant line with an impairment in Stat3 mitochondrial activity, that is described in Chapter 1. At the same time, I contributed to a preliminary characterization of the crosstalk between Stat3 and GR (Dinarello et al., 2022), and I decided to further analyse the effects of this functional interaction in the mitochondrion (Chapter 2). In parallel, I also took part to the study of Stat3 role in regulating the hypoxia/Hif1 pathway both in zebrafish and mouse embryonic stem cells (Dinarello et al., 2023).