Nuclear Organization and Oncogenesis

Cancer is a disease of gene expression that leads to the progressive transformation of normal cells into malignant and metastatic tumor cells. Aberrant gene expression can result from genetic alterations activating oncogenes or inactivating tumor suppressor genes. In addition to the instructions contained in the DNA, a second level of information, the so-called epigenetic information, has recently emerged as another potent mechanism regulating gene expression that do not involve changes in the genotype. Recent studies provide compelling evidence that incorrect establishment and/or mis-interpretation of this epigenetic information, including DNA methylation, chromatin modifications and noncoding RNA expression,  can also play an important role in cancer, thus informing novel approaches for chromatin therapies aimed at restoring a normal transcriptional program. Our laboratory is interested in studying the cellular and molecular mechanisms underlying normal and pathological cell fates with a particular emphasis on cancer and tissue regeneration. We are investigating the importance of the post-translational modification by the small SUMO protein in chromatin biology and gene expression in response to stress, and understanding how this modification regulates, at the chromatin level, the establishment of the specific gene expression programs underlying cell identity. Notably, we are identifying the proteins modified by SUMO and exploring the functional dynamics of sumoylation during cell fate changes, such as reperogramming to stem cells, trandifferentiation and differentiation in early embryogenesis. We are also developping an integrated genome-wide profiling approach to dissect the molecular bases of hepatocellular carcinoma development in adolescents and young adults. Ultimately, we hope that our research will bring new contributions in understanding the mechanisms that underlie normal and pathological cell plasticity, with a view toward therapeutic strategies seeking to manipulate sumoylation levels in regenerative medicine and cancer treatment.