Chiara Lanzuolo

In the last years innovative high-throughput-based genome conformational analysis combined with advanced imaging revealed that each chromosome is folded in a highly organized fashion and occupies specific territories in the nucleus, ensuring adequate regulation of gene expression and the maintenance of genome integrity. In recent years, what is emerging is that, besides the plasticity of the chromatin fundamental for fine-regulated process, the nuclear architecture can also influence important cellular processes and is a hallmark of the healthy cell. In several pathologies, the genome organization is often compromised in parallel to an aberrant nuclear morphology, which in some cases is used by cyto-pathologists in their official diagnosis as an indicator of malignancy. However, the hierarchical relationship between nuclear and genome reshaping and molecular mechanisms involved in both aberrant processes are still unknown. My group is devoted in understanding how the genome folding occur in the nuclear space finding the right orientation and nuclear position and how this conformation is then maintained or regulated in dynamic physiological processes in health and in disease. We started studying epigenetic factors known to play a key role in genome folding and function, the Polycomb group (PcG) of proteins. In our recent work we described for the first time a functional and evolutionary conserved crosstalk between the nuclear Lamin A/C and the PcG proteins, required for the maintenance of the PcG repressive functions. We are now committed in understanding the role of PcG/LaminA interplay in physiological processes such as senescence and pathological conditions as cancer and laminopathies, human disorders caused by mutations in Lamin A/C gene. The ultimate objective will be to produce the fundamental knowledge of molecular mechanisms at the basis of genome remodelling in order to stimulate the development of new pharmacological approaches aimed at reverting nuclear aberrations in human disorders.