Wayland W. L. Cheng, M.D., Ph.D.

Assistant Professor

Biochemistry, Biophysics, and Structural Biology Program
Neurosciences Program
Molecular Cell Biology Program

  • 314 273-7958

  • 314 273-7955

  • CSRB 5515

  • wayland.cheng@wustl.edu

  • https://www.wchenglab.org

  • I am interested in the structure and function of neuronal ligand-gated ion channels, and the mechanism of channel modulation by endogenous lipids or exogenous drugs such as general anesthetics.

Research Abstract:

The mammalian cell membrane consists of a heterogenous and dynamic collection of lipids that are important in cell signaling. Neuronal ligand-gated ion channels (LGICs) are expressed within this complex membrane, and are key targets of neuroactive drugs, including general anesthetics and analgesics. Changes in the lipid content of neuronal membranes are fundamentally important in normal and pathologic processes, such as chronic pain and psychiatric diseases, and may also determine sensitivity to drugs such as anesthetics. Moreover, lipids such as steroids, polyunsaturated fatty acids (PUFAs), and phosphoinositides are themselves allosteric modulators of LGIC activity, and have the potential to become novel therapeutics. How various lipids interact with LGICs, and whether lipids alter the binding and effect of other drugs in LGICs is poorly understood.

The overarching goal of my research program is to understand the structural basis of specific lipid binding interactions with LGICs such as the GABA(A) receptor and nicotinic acetylcholine receptor, and to assess the role of these binding events on LGIC pharmacology and function. To pursue this, my lab utilizes a combination of biochemical and biophysical approaches including native ion mobility mass spectrometry, photo-affinity labeling, electrophysiology, cryoEM, and molecular modeling. The long-term goal of this research is to develop detailed structural models of lipid or allosteric modulation of membrane proteins that will inform the design of novel therapeutics.

Selected Publications:

Sugasawa Y, Cheng WWL, Bracamontes JR, Chen ZW, Wang L, Germann AL, Pierce SR, Senneff TC, Krishnan K, Reichert DE, Covey DF, Akk G, Evers AS. Site-specific effects of neurosteroids on GABA(A) receptor activation and desensitization. eLIFE. 2020 Sep 21; 9:e855331. PubMed PMID 32955433; PubMed Central PMCID: PMC7543004.

Tong A, Petroff JT 2nd, Hsu FF, Schmidpeter PA, Nimigean CM, Sharp L, Brannigan G, Cheng WWL. Direct binding of phosphatidylglycerol at specific sites modulates desensitization of a ligand-gated ion channel. eLIFE. 2019 Nov 14; 8:e50766. PubMed PMID 31724949; PubMed Central PMCID: PMC6855808.

Cheng WWL, Chen ZW, Bracamontes JR, Budelier MM, Krishnan K, Shin DJ, Wang C, Jiang X, Covey DF, Akk G, Evers AS. Mapping two neurosteroid-modulatory sites in the prototypic pentameric ligand-gated ion channel GLIC. J Biol Chem. 2018 Feb 23;293(8):3013-3027. PubMed PMID: 29301936; PubMed Central PMCID: PMC5827446. 

Cheng WW, McCoy JG, Thompson AN, Nichols CG, Nimigean CM. Mechanism for selectivity-inactivation coupling in KcsA potassium channels. Proc Natl Acad Sci U S A. 2011 Mar 29;108(13):5272-7. PubMed PMID: 21402935; PubMed Central PMCID: PMC3069191. 

Cheng WWL, D`Avanzo N, Doyle DA, Nichols CG. Dual-mode phospholipid regulation of human inward rectifying potassium channels. Biophys J. 2011 Feb 2;100(3):620-628. PubMed PMID: 21281576; PubMed Central PMCID: PMC3030149.

Last Updated: 4/16/2021 9:36:05 AM

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