1- Chromatin and transcriptional memory
I study the role of chromatin modifications in the propagation of transcriptional states. We have demonstrated the role of Polycomb proteins in coordinating molecular switches capable of recording a brief transcriptional stimulus (Holoch, Wassef et al., 2021). This study has led us to propose a new regulatory model that differs from the previously proposed model that emphasizes read-and-write of histone modifications as the primary mechanism for the propagation of chromatin states. I am currently working to identify other molecular actors of transcriptional memory.
2- Chromatin and tumor development
Numerous mutations of chromatin regulators are found throughout cancers and the impact of these mutations on chromatin and gene expression is often unclear. I have previously addressed this issue focusing on mutations in genes of the Polycomb family. This work (Wassef et al., 2015; Wassef, Luscan et al., 2019) has led to a better understanding of 1- the causal relationships between aberrant expression of chromatin regulators and tumor development and 2- the striking specificity of mutations in Polycomb gene in different types of cancers. I now seek to extend this type of inquiry to other chromatin regulators and to investigate the functional relationships between the different families of regulators in order to develop new therapeutic approaches to target cancers.