Dr. Fan Yang
Associate Professor, Assistant Dean in the School of Basic Medical Sciences
Zhejiang University
“From atoms to animals: Rational design of novel modulators to TRP ion channels for analgesia”
Abstract:
The Transient Receptor Potential (TRP) ion channels serve as thermoreceptors and nociceptors in the human body. To investigate how these channels are activated by temperature and various pain-inducing compounds, we employ a multidisciplinary suite of biophysical techniques. These include patch-clamp recordings, single-particle cryo-electron microscopy, fluorescent non-natural amino acid imaging, and computational modeling.
Our findings reveal that conformational changes in critical residues of TRP channels alter protein-water interactions, which are fundamental to their temperature activation. Conversely, compounds modulate channel activity by binding to specific "hot spots" within the TRP channels.
Drug development targeting TRP channels has been historically challenging due to the side effect of altering body temperature when these channels are directly inhibited. Leveraging our understanding of TRP channel mechanisms, we have rationally designed TRP-targeting peptides, such as s-RhTx and DeC-1.2, which exhibit analgesic effects in animal pain models without impacting body temperature.
Additionally, we have rationally engineered the TRPM8 channel, known for its permeability to calcium ions, to function as a tool for manipulating calcium-dependent cellular activities in the brain to influence animal behavior. We believe that our foundational research on TRP channels will significantly advance translational applications, including the development of innovative drugs and tools.
For more information about Dr. Yang's work.
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