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The Wuthrich Laboratory

Matthew Eddy


Matthew Eddy, Ph.D.

Research Associate

eddym@scripps.edu
phone: +1 858 784 8356
fax: +1 858 784 8014


Research Interests

My current research focuses on elucidating mechanisms of human G protein-coupled receptor (GPCR) signaling. 

GPCRs are involved in nearly every physiological process and are targeted by 30-40% of available drugs.  I am interested in how drugs shape the conformational landscape of human GPCRs and influence their interactions with intracellular protein partners, ultimately resulting in physiological responses.  I have studied the conformational dynamics of the human b2-adrenergic receptor (b2AR) using 19F-NMR in solution, and I have applied 1H-detected NMR experiments to study the structure and dynamics of the human adenosine A2A receptor (A2AAR).  My research also involves the integration of multiple structural techniques, including x-ray crystallography, as well as biophysical assays to obtain deeper insight into GPCR function.

This work builds on my Ph.D. training in solid state magic angle spinning (MAS) NMR.  The aims of this earlier research were development of MAS NMR methodologies and applications to structural characterization of human membrane proteins in lipid bilayers, including the human voltage dependent anion channel (VDAC).

 

Education

2012               Ph.D. in Physical Chemistry, Massachusetts Institute of Technology, Cambridge, MA

2004               B.A. in Chemistry with honors, Oberlin College, Oberlin, OH

                               

Grants and Fellowships

2014-2017       American Cancer Society Postdoctoral Fellowship

2014                National Institutes of Health NRSA Postdoctoral Fellowship (declined)

 

Publications

Eddy MT; Didenko T, Stevens RC, Wüthrich K. “β2-Adrenergic Receptor Conformational Response to Fusion Protein in the Third Intracellular Loop,” Structure (2016) 24, 2190-2197.

Andreas LB; Reese M, Eddy MT, Gelev V, Ni QZ, Miller EA, Emsley L, Pintacuda G, Chou JJ, Griffin RG. “Structure and Mechanism of the Influenza A M218-60 Dimer of Dimers,” J Am Chem Soc. (2015) 137, 14877-14886.

Eddy MT; Su Y, Silvers R, Andreas L, Clark L, Wagner G, Pintacuda G, Emsley L, Griffin RG; “Lipid Bilayer-bound Conformation of an Integral Membrane Beta Barrel Protein by Multidimensional MAS NMR” J Bio NMR (2015) 61, 1-12.

Eddy MT; Andreas L, Teijido O, Su Y, Clark L, Noskov G, Wagner G, Rostovtseva K, Griffin RG; “Magic Angle Spinning Nuclear Magnetic Resonance Characterization of Voltage-Dependent Anion Channel Gating in Two-Dimensional Lipid Crystalline Bilayers” Biochemistry (2015) 54, 994-1005.

Eddy MT; Yu T-Y; “Membranes, Peptides, and Disease: Unraveling the Mechanisms of Viral Proteins with Solid State Nuclear Magnetic Resonance Spectroscopy” Solid State NMR (2014) 61, 1-7.

Su Y; Sarell CJ; Eddy MT; Pashley CL; Radford SE, Griffin RG; “Secondary Structure in the Core of Amyloid Fibrils Formed from Human b2-Microglobulin and its Truncated Variant DN6” J Am Chem Soc (2014) 136, 6313-6325.

Eddy MT, Belenky M, Sivertsen AC, Griffin RG, Herzfeld J; “Selectively Dispersed Isotope Labeling for Protein Structure Determination by Magic Angle Spinning NMR.” J Bio NMR (2013) 57, 129-139.

Daviso, E, Eddy MT, Andreas LB, Griffin RG, Herzfeld J; “Efficient Resonance Assignment of Proteins in MAS NMR by Simultaneous Intra- and Inter-residue 3D Correlation Spectroscopy.” J Bio NMR (2013) 55, 257-265.

Eddy MT, Ong T-C, Clark L, Teijido O, van der Wel PCA, Garces R, Wagner G, Rostovtseva TK, Griffin RG. “Lipid Dynamics and Protein-Lipid Interactions in 2D Crystals Formed with the b-Barrel Integral Membrane Protein VDAC1.” J Am Chem Soc (2012) 134, 6375-6387.

Andreas LB, Eddy MT, Chou JJ, Griffin RG. “MAS NMR of the Drug Resistant S31N M2 Proton Transporter from Influenza A.” J Am Chem Soc (2012) 134, 7215-7218.

Eddy MT, Ruben D, Griffin RG, Herzfeld J. “Deterministic schedules for robust and reproducible non-uniform sampling in multidimensional NMR.” J Mag Res (2011) 214, 296-301.

Bayro MB, Debelouchina GT, Eddy MT, Birkett NB, MacPhee CE, Rosay M, Maas WE, Dobson CM, Griffin RG. “Intermolecular Structure Determination of Amyloid Fibrils with Magic-Angle Spinning and Dynamic Nuclear Polarization NMR.” J Am Chem Soc (2011) 133, 13967-74.

De Paepe G, Lewandowski JR, Loquet A, Eddy MT, Megy S, Bockmann A, Griffin RG. “Heteronuclear proton assisted recoupling.” J Chem Phys (2011) 134, 095101.

Matsuki Y, Eddy MT, Griffin RG, Herzfeld J. “Rapid Three-Dimensional MAS NMR Spectroscopy at Critical Sensitivity.” Angewante Chemie (2010) 49, 9215-18.

Andreas LB, Eddy MT, Pielak RM, Chou JJ, Griffin RG. “Magic Angle Spinning NMR Investigation of Influenze A M218-60: Support for an Allosteric Mechanism of Inhibition.” J Am Chem Soc (2010) 132, 10958-10960.

van der Wel PCA, Eddy MT, Ramachandran R, Griffin RG. “Targeted 13C-13C Distance Measurements in a Microcrystalline Protein via J-Decoupled Rotational Resonance Width Measurements.” ChemPhysChem (2009) 10,1656-63.

Lewandowski JR, De Paepe G, Eddy MT, Struppe J, Maas W, Griffin RG. “Proton Assisted Recoupling at High Spinning Frequencies.” J Phys Chem B (2009) 113, 9062-69.

Lewandoskwi JR, De Paepe G, Eddy MT, Griffin RG. “15N-15N Proton Assisted Recoupling in Magic Angle Spinning NMR.” J Am Chem Soc (2009) 131, 5769-76.

Matsuki Y, Eddy MT, Herzfeld J. “Spectroscopy by Integration of Frequency and Time Domain Information for Fast Acquisition of High-Resolution Dark Spectra.” J Am Chem Soc (2009) 131, 4648-56.

Bayro MB, Ramachandran R, Caporini MA, Eddy MT, Griffin RG. “Radio frequency-driven recoupling at high magic-angle spinning frequencies: Homonuclear recoupling sans heteronuclear decoupling.” J Chem Phys (2008) 128, 052321.

Mehta MA, Eddy MT, McNeill SA, Mills FD, Long JR. “Determination of Peptide Backbone Torsion Angles Using Double-Quantum Dipolar Recoupling Solid-State NMR Spectroscopy.” J Am Chem Soc (2008) 130, 2202-12.

Mehta MA, Fry EA, Eddy MT, Dedeo MT, Anagnost AE, Long JR. “Structure of the alanine dipeptide in condensed phases determined by 13C NMR.”  J Phys Chem B (2004) 108, 2777-80.