Juan Du Molecular basis of temperature sensation and taste perception, and their connections to pain and metabolism

Research Interests

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

Physiological temperature drives TRMPM4 ligand recognition and gating. Hu J, Park SJ, Orozco I, O'Dea G, Ye X, Du J, and Lü W. Nature. Accepted 2024.

Coupling enzymatic activity and gating in an ancient TRPM chanzyme and its molecular evolution. Huang Y, Sushant K, Junuk L, Lü W, and Du J. Nat Struct Mol Bio. In press, 2024.

Molecular interplay of an assembly machinery for nitrous oxide reductase. Muller C, Zhang L, Zipfel S, Topitsch A, Lutz M, Eckert J, Prasser B, Chami M, Lü W, Du J, and Einsle O. Nature. 2022 June 27;608:626.

Structures of the TRPM5 channel elucidate mechanisms of activation and inhibition. Ruan Z, Haley E, Orozco IJ, Sabay M, Myers R, Du J, and Lü W. Nat Struct Mol Bio. 2021 June 24;28:604.

Structures of human pannexin 1 reveal ion pathways and mechanism of gating. Ruan Z, Orozco IJ, Du J, and Lü W. Nature. 2020 June 03;584:646.

The structures and gating mechanism of human calcium homeostasis modulator 2. Choi W, Clemente N, Sun W, Du J, and Lü W. Nature. 2019 November 27;576:163.

Architecture of the TRPM2 channel and its activation mechanism by ADP-ribose and calcium. Huang Y, Winkler PA, Sun W, Lü W, and Du J. Nature. 2018 September 24;562:145.