I am a chemical biologist studying how epigenetic proteins recognize DNA packaging patterns to influence DNA transcription. I use biophysical techniques to study these proteins, called bromodomains, to discover and optimize small molecule probes which can inhibit these interactions. These probe molecules can then be functionalized with a variety of enrichment, visualization, and proteolysis inducing domains to further study the protein of interest.
Small Molecule Catalyzed Degradation of the Bromodomain Containing Protein BPTF
Bromodomains are epigenetic proteins which serve an important role in maintaining chromatin structure by recognizing post-translational modifications on DNA packing proteins called histones. Misregulation of the bromodomain-histone interaction has been implicated in many forms of cancer. Thus far, the best characterized bromodomains belong to one family, the bromodomain and extra-terminal (BET) family bromodomains. We seek to study a non-BET family bromodomain containing protein called BPTF (bromodomain PHD finger transcription factor). Recently, our lab discovered a small molecule which binds to the bromodomain of BPTF. I have synthesized a small library of analogs to develop the structure activity relationship of this molecule with the aim of developing a higher affinity probe. Using this small molecule scaffold along with a PROTAC (proteolysis targeting chimera) technique, we are synthesizing bifunctional small molecules capable of catalytically degrading BPTF. This approach, along with parallel efforts in discovering and developing potent small molecule inhibitors of the BPTF bromodomain, will elucidate both the role of the entire BPTF protein along with the role of solely its bromodomain in breast and lung cancer.