This group dives deep into the basic biochemistry and biological functions of key enzymes (e.g., acetyl-transferases, deacetylases, and methyltransferases) that can affect chromatin. These detailed enzyme mechanisms require careful investigation of protein structure and function, even to the level of specific amino acids or the movements of single atoms. This crucial work allows us to understand how and when these enzymes are activated or inhibited, and gives us clues on how to use these properties to improve human health. Specific projects aim to inhibit methyltransferases involved in oncogenesis and to enhance the activity of deacetylases involved in promoting longevity.
In this group, our goal is to understand how harmful and beneficial alterations to metabolism affects the cellular network of gene expression. To do so, we employ mouse models, ChIP-Seq, immunoblotting, and cutting-edge mass spectrometry (as well as many other forms of big data!) to understand how changes from diet to disease state affect chromatin. This can take the form of studying the ripple effects created by removing a specific metabolite or protein, or studying the more subtle changes that can occur with changes in diet or lifestyle. Projects in this area include: investigating how a specific sirtuin (i.e., protein deacetylase) affects mouse fitness and longevity, understanding how fluctuations in central metabolites affect chromatin, and uncovering how microbial metabolism affects the host epigenome.