Post-translational modification of histone proteins, including lysine methylation and acylation, regulate gene expression through recruitment of reader proteins to the nucleosome. Dysregulation of these events is prevalent in a wide range of diseases, such that there is much interest in characterizing these modifications and their binding partners.  We have used both supramolecular chemistry and protein engineering approaches to study the protein-protein interactions that are mediated by these post-translational modifications and to develop new tools to sense them.

The fidelity of intracellular signaling pathways requires that cells control the production of signaling agents in space and in time. Phosphatidic acid (PA) is both a central phospholipid biosynthetic intermediate and a multifunctional lipid second messenger produced at several discrete subcellular locations. The modes of action of PA can differ based on upstream stimulus, biosynthetic source, and site of production. How cells regulate the local production of PA to direct diverse signaling outcomes remains elusive.

Title: How Chemistry Can Change Your Fate: From Microbiome Metabolism to Genome-wide Damage