Youzhong Guo, Ph.D., is interested in membrane protein structural biology and structure-based drug discovery. Membrane proteins play numerous crucial roles in all living organisms, such as nutrient transport, photosynthesis, rhythmic heart beating and human brain-conscious activities. Because of their unique location on the cell membrane, they are accessible to both small-molecule drugs and large-size biologics, such as therapeutic antibodies. Not surprisingly, more than 60% of modern drug targets are membrane proteins.

Guo and colleagues have been developing a novel native cell membrane nanoparticles system (NCMN system). This is a breakthrough technology for membrane protein research. Traditionally, small molecule detergents have to be used to solubilize and stabilize membrane proteins; however, detergents often damage the protein-lipid interactions that are often essential for the structural stability and functionality of membrane proteins. Instead of using small molecule detergents, the NCMN system deploys membrane-active polymers to fabricate membrane proteins together with their associated native lipids as nanoparticles. The resulting NCMN particles retain membrane proteins in their natural states as they are originally on the cell membrane.

Guo and his research team mainly utilize single-particle cryo-EM technology and X-ray crystallography to solve the atomic structure of membrane proteins to facilitate the understanding of the molecular mechanisms of membrane protein enzymes, transporters, channels and receptors.

Current membrane protein projects in Guo’s laboratory include:

• Structure and enzyme activity of the TSPO proteins 
• Structure and gating mechanism of TRP channels 
• Structure and gating mechanism of mechanosensitive channels
• Structure and gating mechanism of Cys-loop ligand-gated ion channels 
• Structure and gating mechanism of gap-junctions
• Structure and active mechanism of ABC transporter 
• Structure and active mechanism of SLC transporters
• Structure and active mechanism of GPCRs
• Structure and active mechanism of receptor tyrosine kinases 
• Structure-based drug discovery for cancers, heart diseases, diabetes, neurodegenerative diseases, infectious diseases

• Ph.D. (Medicinal Chemistry), University of Texas at Austin