Welcome to the Yin research group at the University of Colorado at Boulder!
We are a young group at CU. Our interests lie at the interface of chemistry and biology with particular focuses on structure-based drug design and membrane protein regulation. Current projects include:
1. Drug Discovery: identifying potential therapeutics that inhibit opioids-induced glial cell activation
Pain remains a significant public health issue with two-thirds of patients achieving little to no pain relief from the myriad of currently available pharmacotherapies and dosing regimens. The use of opioid (e.g. morphine) pharmacotherapies produces several rewarding and reinforcing side effects, which result in the drugs’ diversion to abuse settings. Glial cells have been found to play a critical role in initiating and maintaining increased nociception in response to peripheral nerve injury. The opioids-induced glial cell activation attenuates opioid-induced pain suppression and enhances the development of opioid tolerance and dependence, the drug reward, and other negative side effects such as respiratory depression. We are interested in employing structure-based drug design and high-throughput screening techniques to identify novel small-molecule inhibitors of the cell surface receptors that regulate glical cell activation. The identified agents will potentially serve as therapeutics that suppresses opioid-dependence and tolerance.
2. Biotechnology Development: Protein engineering for targeting membrane receptors
Protein transmembrane domains regulate many pivotal biological processes, including cell signal transduction, cancer development, ion transmission, and membrane protein folding. However, the molecular recognition in membranes is little understood due to the lack of available probes with high affinity and specificity. Conventional tools such as antibodies are unable to bind to the transmembrane regions of membrane proteins. A second project in our lab is to develop exogenous peptide and small-molecule agents that target transmembrane helices. Using these agents, we can study these important membrane protein-protein interactions, thereby further our understanding of molecular recognition in membranes. As a proof-of-principle, we plan to develop novel peptide/peptidomimetic reagents to target the first transmembrane domain (TMD-1) of latent membrane proteins 1 (LMP-1) found on the Human herpesvirus. These designed peptides will be used to study TMD-1-mediated LMP-1 activation. The findings from these studies will lay the groundwork for the discovery of new pharmaceutical agents with which we can prevent, diagnose, and treat herpesvirus-dependent cancers.
