Wei Lü Professor

Research Summary:

The Du lab and Lü lab are dedicated to unraveling the complexities of sensory perception—how the human body detects external stimuli, transmits these signals to the brain, and elicits appropriate responses through the intricate network of neuronal ion channels. A particular focus of our work is on understanding the biophysical mechanisms underlying temperature sensation and taste perception. These fundamental aspects of sensory processing offer profound insights into human physiology and potential therapeutic avenues for a range of conditions. 
We employ multidisciplinary biophysical methodologies, such as cryo-electron microscopy (Cryo-EM) and patch-clamp electrophysiology, to visualize these sensory ion channels and receptors at an atomic level and understand their role in signal transduction processes critical for sensory perception. 
Our long-term goals are to 1) Elucidate the molecular basis of temperature sensation and taste perception, and explore their connections to pain and metabolism, respectively; 2) Understand how temperature affects protein dynamics and ligand recognition; 3) Study how temperature influences taste perception (thermotaste) at mechanistic and animal level; 4) Develop novel therapeutics for pain therapy and metabolic diseases using structure-guided drug design approaches.

 

Selected Publications:

(*: co-corresponding author; #: co-first author)

Hu J, Park S.J., Orozco I, O’Dea G, Ye X, Du J*, Lü W*. Physiological temperature drives TRPM4 ligand recognition and gating. Nature, accepted, 2024.

Huang Y, Sushant Kumar, Junuk Lee, Lü W* & Du J*. Coupling enzymatic activity and gating in an ancient TRPM chanzyme and its molecular evolution. Nat Struct Mol Biol, in press, 2024.

Ruan Z#, Haley E#, Orozco IJ#, Sabat M, Myers R, Du J*, Lü W*. Structures of the TRPM5 channel elucidate mechanisms of activation and inhibition. Nat Struct Mol Biol 28, 604-613, 2021.

Ruan Z#, Osei-Owusu J#, Du J, Qiu Z*, Lü W*. Structures and pH-sensing mechanism of the proton-activated chloride channel. Nature 588, 350-354, 2020.

Ruan Z, Orozco I. J., Du J*, Lü W*. Structures of human pannexin 1 reveal ion pathways and mechanism of gating. Nature 584, 646-651, 2020.

Choi W#, Clemente N#, Sun W, Du J*, Lü W*. The structures and gating mechanism of human calcium homeostasis modulator 2. Nature 576, 163-167, 2019.

Huang Y, Winkler PA, Sun W, Lü W* & Du J*. Architecture of the TRPM2 channel and its activation mechanism by ADP-ribose and calcium. Nature 562, 145-149, 2018.

Winkler PA#, Huang Y#, Sun W#, Du J, Lü W. Electron cryo-microscopy structure of a human TRPM4 channel. Nature 552, 200-204, 2017.