Our Research
Beyett Lab Publications (Google Scholar)
Classic molecular pharmacology is the study of how current therapeutics work to combat disease. While we remain committed to expanding our understanding of drug mechanism of action, we’re also asking the important question of what’s next? Modern molecular pharmacology aims to lay the foundation for the development of next-generation medicines through the identification of novel drug targets and validation of new therapeutic strategies. This is often accomplished through the creative application of chemical methods to biological systems – chemical biology.
We are generally interested in kinases and phosphatases, which play opposing roles in maintaining balance in many signaling cascades and are often mutated or dysregulated in cancer. Our research is focused on 1) new kinase therapeutic strategies and 2) how phosphatases are regulated by protein-protein interactions.
Targeting Oncogenic Kinases
Two is better than one, right? That is one of several questions we aim to answer when it comes to kinase therapeutics. While combination drug regimens are commonplace in cancer therapy, simultaneous “dual-targeting” or “double-drugging” of kinases is an emerging therapeutic strategy that we are exploring. We are especially excited about the use of targeted protein degraders (e.g. PROTACs) in combination drug therapies for EGFR and other receptor tyrosine kinases.
We also aim to think outside the box, where the box is the kinase active site. Much like a factory machine, there’s many moving parts to a kinase, and figuring out all the places where you can jam a wrench to stop the machine can lead to the discovery of new types of inhibitors. Allosteric kinase inhibitors do just that, and we are working to discover novel allosteric inhibitors for uncommon kinase variants in lung cancer via high-throughput screening at the Emory Chemical Biology Discovery Center. It is likely that these new allosteric inhibitors can be used in combination with existing therapeutics for the more safe and effect treatment of lung cancers.
Probing Regulators of Immune Cell Signaling
Physiology requires balance and understanding this balance can open new therapeutic doors. Phosphatases often act as a brake to regulate kinase signaling pathways, preventing runaway signaling that can lead to disease. We are studying the CABIT domain-containing family of proteins, which regulate phosphatases in a variety of important cellular signaling pathways. We are especially interested in the protein THEMIS, which influences the development of T cells and has emerging relevance to cancer immunotherapy. We are using biochemical and biophysical methods to understand the structure and function of THEMIS and how it interacts with and regulates phosphatases in the immune system. A major goal is to develop chemical probes for THEMIS with which to explore the potential of modulating these protein-protein interactions for therapeutic benefit.
Collaboration
With expertise in protein biochemistry, X-ray crystallography, structure-based drug design, high-throughput screening, and molecular pharmacology, we are happy to assist with projects. We have numerous established collaborations within Emory and beyond. Please contact us if you would like to work together on a project or would like technical advice. We are always happy to share plasmids, protocols, and other common reagents.
Beyett Lab 