How do transcription factors engage their motifs in a chromatinized genome?
My lab focuses on the fundamental workings of DNA binding proteins, particularly transcription
and repair factors. We are interested in how these proteins operate in the context of chromatin,
where nucleosomes frequently gate access to DNA and play an important role in repair and
gene regulation. A particular focus of the lab is on studying the link between chromatin binding
factors and ubiquitin biology. By dissecting the detailed mechanism of molecular glue drugs,
a novel class of small molecule therapeutics that induce proximity between a protein and a
ubiquitin ligase, we have provided the molecular basis of how the drug thalidomide (also
known as Contergan) successfully degrades transcription factors. Recent work from my
laboratory showed how small molecules can induce other unexpected neo-morphic
interactions between proteins, a previously unanticipated phenomenon intrinsic to many
known drugs. These studies offer insight into the fundamental workings of genome-bound
protein machines, the forces that govern protein-protein interactions, and the ways in which
protein interactions can be reprogrammed by small molecules.