SC13: GPCR Structure-Based Drug Discovery
THURSDAY, SEPTEMBER 27, 7:00 - 9:30 PM
Room: Gardner 

Recent breakthroughs in obtaining high-resolution structures of G Protein-Coupled Receptors (GPCRs) by both X-ray crystallography and Cryo-EM technology, are rapidly impacting the pharmaceutical industry. In this short-course, Dr. Wu will review how GPCR structures elucidated to date have informed our current understanding of GPCR function. She will also provide examples of how GPCR structural information is being applied to guide rational approaches for GPCR drug discovery. Dr. Eddy will review how this structural information is complemented by various biophysical techniques that provide information on GPCR dynamics and function. He will discuss new biophysical approaches and share recent examples that illustrate applications for drug discovery.

Topics to be covered:


  • Methodologies for the characterization and crystallization of GPCRs
  • Review of x-ray crystallographic and cryoEM GPCR structures and their lessons
  • Biophysical tools (NMR, fluorescence spectroscopy, EPR, SPR and computational approaches) for observing function-related conformational dynamics of GPCRs
  • Implications for drug discovery, especially regarding allosteric modulation by small molecules, ions, and engineered partner proteins

Instructors:

Matthew Eddy, Ph.D., Assistant Professor, Chemistry, University of Florida

Huixian Wu, Ph.D., Principal Scientist, Structural and Molecular Sciences, Discovery Sciences, Pfizer Inc. Groton

Eddy_MatthewMatthew Eddy, Ph.D., Assistant Professor, Chemistry, University of Florida

Dr. Matthew Eddy is a physical chemist who specializes in the investigation of the structure and conformational dynamics of membrane proteins, including G Protein-Coupled Receptors, using nuclear magnetic resonance (NMR). Dr. Eddy received his Ph.D. from the the laboratory of Professor Robert Griffin at the Massachusetts Institute of Technology. During his Ph.D., Eddy developed new methodologies for using NMR in the solid state to determine structures of membrane proteins in cellular-like environments. Following his PhD, Dr. Eddy joined the laboratories of Professors Raymond Stevens and Kurt Wüthrich at The Scripps Research Institute and University of Southern California as an American Cancer Society Postdoctoral Fellow, applying an integrative structural biology approach to study human G protein-coupled receptors (GPCRs) and focusing on applications of NMR to understand GPCR allosteric functions. Dr. Eddy has authored or coauthored over 25 peer-reviewed publications in high-profile scientific journals including Cell, JACS, and Structure.  Dr. Eddy recently started his own laboratory at the University of Florida, developing new approaches to investigate GPCR structure-function relationships directly in cellular environments.

Wu_HuixianHuixian Wu, Ph.D., Crystallography Lab Head, Principal Scientist, Structural and Molecular Sciences, Discovery Sciences, Pfizer Inc.

Dr. Huixian Wu received her Ph.D in Structural Biology and Chemistry from the Scripps Research Institute (La Jolla, CA) in the laboratory of Prof. Raymond C. Stevens. While in Stevens lab, Dr. Wu focused on G protein-coupled receptor (GPCR) crystallography where she determined the crystal structures of several important human GPCRs, including the k-opioid receptor, metabotropic glutamate receptor, and smoothened receptor. After completing her Ph.D, Dr. Wu joined Prof. Stuart L. Schreiber’s laboratory in the Broad Institute of Harvard and MIT (Cambridge, MA) for postdoctoral research, working on structure-based drug development (SBDD) targeting inflammatory bowel diseases. Currently, Dr. Wu is a Principal Scientist leading a Crystallography lab at Pfizer (Groton, CT). Her lab is supporting SBDD of diverse therapeutic targets across multiple disease areas in Pfizer.

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