Silvia Monticelli, Group Leader
Our lab is interested in understanding epigenetic mechanisms of regulation of gene expression, which might be important for the development of a number of immunological diseases, from neoplasia of mast cells (mastocytosis) to autoimmune disorders such as multiple sclerosis. Epigenetic inheritance is usually independent from alterations in the DNA sequence encoding a given gene, and while in the most stringent definition this includes mostly DNA methylation (and its derivatives), it can also more broadly include histone modifications and even microRNAs (miRNAs). Our lab is mostly interested in understanding the role of DNA methylation dynamics in regulating cell differentiation and function, as well as the interplay between the DNA methylation machinery and miRNA expression. MiRNAs are small non-coding RNAs that have emerged as key post-transcriptional regulators in a wide variety of organisms and biological processes. Because each miRNA can regulate expression of a distinct set of genes, miRNA expression can shape the repertoire of proteins that are expressed during development, differentiation or disease. Accordingly, genetic ablation of the miRNA machinery, as well as loss or dysregulation of certain individual miRNAs, severely compromises immune development and leads to immune disorders such as autoimmunity and cancer. In our lab we are studying the role of both DNA methylation and miRNAs in the differentiation and function of cells of the immune system, with a special focus on T lymphocytes and mast cells. Besides being of fundamental relevance to our understanding of cell differentiation and gene regulation, elucidation of the molecular mechanisms underlying these processes have substantial potential for clinical application in the treatment of malignancies and autoimmune diseases.