Fred Van Leeuwen

Biography

Fred van Leeuwen has a longstanding interest in how non-genetic changes can have long-term consequences for cellular function. He has worked in different fields of epigenetics; starting by investigating an unusual DNA modification in trypanosomes as a graduate student, and currently using yeast as a powerful model system and mouse cancer models to discover new mechanisms of epigenetic regulation. His lab currently focuses on two key issues in epigenetics and teams up with international collaborators to tackle these problems. One key question is the regulation of post-translational histone modifications, small chemical marks that influence genome packaging and function. Using yeast genetic screens, genetic engineering, proteomics, and mathematical modeling the van Leeuwen lab determined the mechanism of methylation by Dot1, a conserved histone methyltransferase that is involved in certain human leukemias. Knowledge of the fundamental enzymatic properties explains modes of regulation, predicts functions of the histone methylation states, and suggests that this mark is not a memory mark but instead may act as a cellular timer. The other key question is whether and how histone proteins contribute to inheritance. By developing novel methods to track old and new proteins in living cells and taking advantage of unique properties of budding yeast the van Leeuwen lab has been able to determine several key parameters for epigenetic inheritance. The new findings suggest that histone inheritance is imprecise and that histones may walk along transcribed regions of the genome.    

Research Interest

Fred van Leeuwen and his team are currently developing novel barcode screening strategies to identify the mechanisms controlling epigenome dynamics and inheritance to unravel the biological roles of these poorly understood layers of epigenetic regulation.