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 aging, two processes that share many molecular pathways. We are investigating the importance of the post-translational modification by SUMO in chromatin biology and gene expression in healthy and cancer cells and understanding how this modification regulate cell homeostasis and plasticity. We are also developping a multidimensional, integrated genome-wide profiling approach to dissect hepatocellular carcinoma. Finally, we are identifying chromatin and gene network changes during cellular senescence, a stable cell cycle arrest impacting both physiological and pathological aging processes. Ultimately, we hope that our research will bring new contributions in understanding the mechanisms that underlie cancer and the biology of aging with a view toward therapeutic strategies seeking to manipulate defined genes and pathways such as sumoylation.