Dr. Hang (Hubert) Yin is an assistant professor of chemistry and biochemistry and a member of the Colorado Initiative in Molecular Biotechnology at the University of Colorado Boulder. He is also a member of the University of Colorado Cancer Center Developmental Therapeutics Program. His research focuses on building new tools to probe inaccessible proteins that play a role in cancer development—specifically, lymphomas and leukemia.
Yin: We plan to develop novel biotechnological tools to probe and study the integral membrane protein Latent Membrane Protein-1, which plays an important role in cancer development.
Conventional thought has it that it is difficult, if not impossible, to develop specific probes for these proteins as they are buried deep in cell membranes. Structure-based drug designs cannot work against certain membrane proteins because scientists don’t know how those proteins function, so they cannot target them.
We believe we can move beyond that conventional thinking, or comfort zone, to unlock these important drug targets using a combination of screening and structure-based design technologies. We hope to come up with highly specific and selective peptide probes that can actually target these proteins through structures that were previously regarded as impenetrable. It’s like trying to awaken a person in a deep sleep at the bottom of the ocean by poking him with a submarine. Despite a daunting challenge like this, the preliminary studies suggest that we may succeed.
C3: Your project focuses on the Epstein-Barr virus (EBV). How can this common virus be useful in uncommon research?
Yin: Although EVB affects more than 90 percent of humans and its infections are mostly benign, it can come into play in various types of lymphomas. We know EBV hijacks certain white blood cells and makes them cancerous, but we don’t really know how it happens because we don’t have a tool to probe the protein that regulates that virus’s activities.
When my colleague and peer Cancer Center member, Dr. Jennifer Martin, approached me to study this problem, we realized that this could provide an ideal model system to which we can use computationally designed probes. I had to say that this was a pretty wild idea as, to the best of our knowledge, no previous work has been done to target a complex integral membrane protein using externally derived agents.
C3: How does your work combine protein engineering with chemistry and biochemistry?
Yin: My lab currently has about 20 researchers with various backgrounds ranging from computational simulations, peptide and protein biochemistry, organic synthesis, molecular biology, to cell biology. For the LMP-1 project, we have been using an array of different techniques, including computational simulation, spectroscopies and organic synthesis to study cancer biology. With these powerful tools in hand, we can address daunting questions that were inaccessible previously.
However, the integration process is by no means painless. Something intriguing and rational to a biochemist may seem absurd to a computer scientist and vice versa. However, the CU Cancer Center and Colorado Initiative in Molecular Biotechnology have done an excellent job to facilitate such collaborations as the leaders do have the vision and strong faith in multidisciplinary research.
C3: You completed your doctorate at Yale and a post-doc fellowship at the University of Pennsylvania School of Medicine. What brought you to Colorado?
Yin: I grew up in Beijing, which is a pretty overwhelming place. When I first came to visit Colorado, I fell in love with this peaceful land immediately. Then I had a chance to join the Colorado Initiative in Molecular Biotechnology and the Department of Chemistry and Biochemistry at CU. CIMB is a place with such exciting research and entrepreneurial tradition, and the Cancer Center offers a plethora of productive collaborations. The possibility for cutting-edge research is only limited by your imagination.