WELCOME TO THE CHENG LAB
Our aim is to understand the molecular mechanisms of allosteric modulation of ligand-gated ion channels.
Neuronal ligand-gated ion channels such as the GABA(A) receptor are the essential determinants of synaptic neurotransmission, and the targets of many therapeutic agents including anesthetics. There is emerging evidence that lipids modulate ligand-gated ion channels by binding to specific sites, and that exogenous modulators such as anesthetics bind to the same or overlapping sites. Our current focus is to define the interactions of lipids and small molecule drugs in these channels, and the effects of these interactions on protein structure and function.
We use a multidisciplinary approach to study lipid and small molecule modulation of ligand-gated ion channels that includes the following techniques:
Native ion mobility mass spectrometry
Chemical biology approaches including photo-affinity labeling
Patch-clamping and ion flux measurements of channels reconstituted in liposomes
Single particle cryo-EM analysis for structure determination
A Collaborative & Diverse Group
WAYLAND W. L. CHENG, MD PHD
I am an Assistant Professor in the Division of Basic Science Research in the Department of Anesthesiology at Washington University in St. Louis. I received an MD/PhD from Washington University in molecular and cellular biology, and completed my doctoral work with Colin Nichols investigating phospholipid modulation of inward rectifying potassium channels. I then completed training in Cardiothoracic Anesthesiology, and postdoctoral work with Alex Evers investigating neurosteroid and cholesterol interactions with pentameric ligand-gated ion channels. My research focuses on mechanisms of lipid regulation of ion channels. We utilize electrophysiological techniques, stopped-flow fluorescence measurements, photo-affinity labeling, native mass spectrometry, and single-particle cryo-EM.
EQUIPMENT & FACILITIES
We are equipped with mass spectrometers for native ion mobility MS analysis as well as top-down and middle-down MS analysis of membrane proteins. We have an electrophysiology rig set-up for liposome patch-clamp recordings and an SX-20 stopped-flow fluorimeter for liposome flux assays. We also have access to the Biomedical Mass Spectrometry Resource, and the Center for Cellular Imaging (WUCCI) for cryo-EM analysis.
WATERS SYNAPT G1 MASS SPECTROMETER
We are equipped with this first-generation Waters Q-ToF with T-wave ion mobility separation to perform native ion mobility MS analysis of membrane proteins.
ELECTROPHYSIOLOGY RIG FOR PATCH-CLAMPING
ROCKET ESPRESSO GIOTTO EVOLUZIONE R ESPRESSO MACHINE
From the seat of Italian fashion, the Rocket Espresso Giotto Evoluzione R brings the best of single boiler technology to Cheng Lab. Encased in polished Italian steel, the Giotto Evo's 1.8-liter heat-exchange boiler offers simultaneous brewing and steaming without the need for multiple heating elements or complex control boards. With an eye on design and the features to back it up, the Giotto Evo makes a fine coffee companion for all those late night research sessions. (St. Louis' best Kaldis coffee always on hand.)
The Washington University Center for Cellular Imaging is equipped with two Titan G3 Krios 300kV cryo-transmission electron microscopes for single particle cryo-EM tomography of vitrified samples. Our laboratory also has two GPU workstations for rapid analysis of single particle cryo-EM data.
BIOMEDICAL MASS SPECTROMETRY RESOURCE
This mass spectrometry resource in the Washington University Danforth campus is equipped with numerous mass spectrometers including instruments for high mass (native or intact protein) measurements such as the Thermo Exactive Plus EMR.
THERMO ELITE ORBITRAP MASS SPECTROMETER
In collaboration with Alex Evers, we have access to this Orbitrap mass spectrometer equipped with a Thermo Dionex nano-LC system for high sensitivity middle-down and bottom-up MS analysis of membrane proteins.
SX-20 STOPPED-FLOW FLUOROMETER
January 4, 2022
POLYUNSATURATED FATTY ACIDS INHIBIT A PENTAMERIC LIGAND-GATED ION CHANNEL THROUGH ONE OF TWO BINDING SITES
Dietzen NM, Arcario MJ, Chen LJ, Petroff JT 2nd, Moreland KT, Kathiresan K, Brannigan G, Covey DF, Cheng WWL. eLife. 11:e744306
January 4, 2022
Cheng WWL, Acario MJ, Petroff JT 2nd. Frontiers in Physiology. 12(2365): 798102.
June 9, 2021
Nagele P et al. Sci Transl Med. 13(597):eabe1376.
September 21, 2020
Sugsawa 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. eLife. 9:e55331.
April 14, 2020
Petroff JT 2nd, Tong A, Chen LJ, Dekoster GT, Khan F, Abramson J, Frieden C, Cheng WWL. Anal Chem. 92(9): 6622-6630.
November 14, 2019
DIRECT BINDING OF PHOSPHATIDYLGLYCEROL AT SPECIFIC SITES MODULATES DESENSITIZATION OF A LIGAND-GATED ION CHANNEL.
Tong A, Petroff JT 2nd, Hsu FF, Schmidpeter PA, Nimigean CM, Sharp L, Brannigan G, Cheng WWL. eLife. 8:e50766.
June 5, 2019
MULTIPLE NEUROSTEROID AND CHOLESTEROL BINDING SITES IN VOLTAGE-DEPENDENT ANION CHANNEL-1 DETERMINED BY PHOTO-AFFINITY LABELING
Cheng WWL, Budelier MM, Sugasawa Y, Bergdoll L, Queralt-Martín M, Rosencrans W, Rostovtseva TK, Chen ZW, Abramson J, Krishnan K, Covey DF, Whitelegge JP, Evers AS. Biochim Biophysical Acts Mol Cell Biology Lipids. 1864(10): 1269-1279.
May 28, 2019
Sugasawa Y, Bracamontes JR, Krishnan K, Covey DF, Reichert DE, Akk G, Chen Q, Tang P, Evers AS, Cheng WWL. J Steroid Biochem Mol Biol. 192:105383.
March 7, 2019
Chen ZW, Bracamontes JR, Budelier MM, Germann AL, Shin DJ, Kathiresan K, Qian MX, Manion B, Cheng WWL, Reichert DE, Akk G, Covey DF, Evers AS. PLoS Biol. 17(3):e3000157.
Budelier MM, Cheng WWL, Chen ZW, Bracamontes JR, Sugasawa Y, Krishnan K, Mydock-McGrane L, Covey DF, Evers AS. Biochim Biophys Acta Mol Cell Biol Lipids. 1864(2):128-136.
February 23, 2018
MAPPING TWO NEUROSTEROID-MODULATORY SITES IN THE PROTOTYPIC PENTAMERIC LIGAND-GATED ION CHANNEL GLIC.
Cheng WWL, Chen ZW, Bracamontes JR, Budelier MM, Krishnan K, Shin DJ, Wang C, Jiang X, Covey DF, Akk G, Evers AS. J Biol Chem. 293(8):3013-3027.
June 2, 2017
PHOTOAFFINITY LABELING WITH CHOLESTEROL ANALOGUES PRECISELY MAPS A CHOLESTEROL-BINDING SITE IN VOLTAGE-DEPENDENT ANION CHANNEL-1.
Budelier MM, Cheng WWL, Bergdoll L, Chen ZW, Janetka JW, Abramson J, Krishnan K, Mydock-McGrane L, Covey DF, Whitelegge JP, Evers AS. J Biol Chem. 292(22):9294-9304.
February 21, 2017
CLICK CHEMISTRY REAGENT FOR IDENTIFICATION OF SITES OF COVALENT LIGAND INCORPORATION IN INTEGRAL MEMBRANE PROTEINS.
Budelier MM, Cheng WW, Bergdoll L, Chen ZW, Abramson J, Krishnan K, Qian M, Covey DF, Janetka JW, Evers AS. Anal Chem. 89(4):2636-2644.
June 7, 2013
D'Avanzo N, Lee SJ, Cheng WW, Nichols CG. J Biol Chem. 288(23):16726-37.
March 29, 2011
Cheng WW, McCoy JG, Thompson AN, Nichols CG, Nimigean CM. Proc Natl Acad Sci U S A. 108(13):5272-7.
Kurata HT, Cheng WW, Nichols CG. Methods Mol Biol. 720:113-26.
February 2, 2011
Cheng WWL, D'Avanzo N, Doyle DA, Nichols CG. Biophys J. 100(3):620-628.
D'Avanzo N, Cheng WW, Wang S, Enkvetchakul D, Nichols CG. Channels (Austin). 4(3):139-41.
November 26, 2010
DIRECT AND SPECIFIC ACTIVATION OF HUMAN INWARD RECTIFIER K+ CHANNELS BY MEMBRANE PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE.
D'Avanzo N, Cheng WW, Doyle DA, Nichols CG. J Biol Chem. 285(48):37129-32.
December 24, 2010
FUNCTIONAL COMPLEMENTATION AND GENETIC DELETION STUDIES OF KIRBAC CHANNELS: ACTIVATORY MUTATIONS HIGHLIGHT GATING-SENSITIVE DOMAINS.
Paynter JJ, Andres-Enguix I, Fowler PW, Tottey S, Cheng W, Enkvetchakul D, Bavro VN, Kusakabe Y, Sansom MS, Robinson NJ, Nichols CG, Tucker SJ. J Biol Chem. 285(52):40754-61.
EXPRESSION AND PURIFICATION OF RECOMBINANT HUMAN INWARD RECTIFIER K+ (KCNJ) CHANNELS IN SACCHAROMYCES CEREVISIAE.
D'Avanzo N, Cheng WW, Xia X, Dong L, Savitsky P, Nichols CG, Doyle DA. Protein Expr Purif. 71(1):115-21.
Cheng WW, Enkvetchakul D, Nichols CG. J Gen Physiol. 133(3):295-305.
Cheng WW, Tong A, Flagg TP, Nichols CG. Channels (Austin). 2(1):34-8.
July 16, 2007
Kurata HT, Cheng WW, Arrabit C, Slesinger PA, Nichols CG. J Gen Physiol. 130(2):145-55
Department of Anesthesiology
660 South Euclid Ave
Saint Louis, MO 63110