Constance Alabert

Most of the proteins involved in the duplication of chromatin-based information are instrumental for normal development and are often found deregulated in human diseases such as cancer, premature aging, or intellectual disabilities. To understand epigenetic memory, we are using time resolved replication coupled mass spectrometry, from a couple of minutes after the passage of the fork to multiple subsequent cell cycles. This strategy enables us to uncover previously undetected interplay between chromatin-based pathways. This is a crucial step in advancing our understanding of the mechanisms behind the stability of epigenetic information under normal conditions and its disruption in disease contexts.

DNA replication is required for successful cell fate transitions across diverse physiological, experimental, and pathological contexts involving factors often deregulated in human cancer and intellectual disabilities. The underlying mechanisms are fundamental for our understanding of tissue specification and organ homeostasis but are poorly understood. We have discovered a profound and rapid rewiring of the proteins that are recruited around DNA replication forks, upon differentiation of human induced pluripotent stem cells (iPSCs) into mesoderm. We are exploring how DNA replication contributes to the mechanistic diversity of cell fate transitions.