The research topic of our group concerns the study of transcriptional and post-transcriptional mechanisms of regulation of gene expression in cells of the immune system. The general goal is to extend our knowledge of the mechanisms that regulate immune cell differentiation, proliferation and functions and to disclose networks of interaction between epigenetic modifications, transcription factors, microRNAs (miRNAs) and their targets.
Epigenetic and epitranscriptomic modifications are covalent modifications of the genomic DNA and the mRNA that contribute to the regulation of gene expression. For instance, we found that the deletion of Dnmt3a, an enzyme responsible for DNA methylation, leads to the hyper-activation of cells of the immune system, which in turn can lead to tissue damage and disease (Leoni C. et al. PNAS 2017). In general, we are interested in uncovering mechanisms that are on the one hand important for proper immune cell function, but on the other hand may lead to excessive cell proliferation or inappropriate, damaging responses, for example in the context of autoimmune diseases (Emming, Bianchi, Polletti et al. Nature Immunology 2020; Chirichella, Bianchi, Dzafo et al. PLoS Biology 2022).
Currently, we are interested in mechanisms of post-transcriptional regulation involving RNA methylation and RNA-binding proteins, as well as in understanding the mechanism of action of transcription factors that are specifically associated to inflammatory T cell responses.
Status: in progress
The general aim is to understand how post-transcriptional regulatory mechanisms mediated by RNA-binding proteins (RBPs) affect immune cell responses. Currently, we are focusing on selected classes of RBPs to determine their role in restraining inflammatory responses both in T lymphocytes as well as in mast cells of the innate immune system. Additionally, in collaboration with the lab of Vigo Heissmeyer (LMU Munich, Germany), we are studying the impact that the m6A methylation has on the expression of inflammatory mRNAs such as those encoding for cytokines.
Status: in progress
Following up on previous work from our lab (Emming, Bianchi, Polletti et al. Nature Immunology 2020), that identified specific transcription factors and signaling molecules associated to a highly pro-inflammatory and potentially pathogenic phenotype of human T lymphocytes, we are now investigating how some of these factors are regulated in humans and may be associated to disease, especially in the context of autoimmunity.