Traynelis Lab
Welcome to the Traynelis Lab
The Traynelis Lab is located within the Department of Pharmacology at Emory University is located in Suite 5001 in the Rollins Research Center on Emory’s campus in Atlanta, Georgia
Professor of Pharmacology and Chemical Biology
Emory University School of Medicine
1510 Clifton Rd. NE
5062 Rollins Research Center
Atlanta, GA 30322
Our Research
We record electrophysiologically from native and recombinant glutamate-gated receptors that mediate synaptic transmission, as well as from excised outside-out patches that contain a single active channel. Our goal is to achieve a molecular understanding of receptor-channel function in the context of the known structure of the channel.
We run a robust drug discovery program in collaboration with Dr. Dennis Liotta in the Chemistry Department at Emory. This has led to the discovery of new pharmacological probes that modulate glutamate and GABA receptors, which we are refining through medicinal chemistry and structure-based design. We focus on both positive and negative subunit-selective allosteric modulators that fine-tune specific circuits. The overarching goal is to validate new therapeutic targets for the treatment of neurological and neuropsychiatric diseases and discover new clinical candidates.
A large number of patients harbor missense genetic variants in the genes encoding glutamate receptor subunits. We carry out a comprehensive functional evaluation of the impact of de novo human mutations on glutamate receptors and interpret these data in relation to clinical phenotypes. We collaborate with the Center for Functional Evaluation of Rare Variants (CFERV) at Emory and Dr. Hongjie Yuan, who is developing multiple knock-in mouse models of human mutations in the GRIN family of genes encoding NMDA receptors.
GRID and GRIN3 genes encode unconventional glutamate receptor subunits (GluD1,2 and GluN3A,B) that do not necessarily act as ligand-gated ion channels in response to agonist binding. We are exploring the mechanisms underlying these receptors using multiple approaches, including the development of subunit-selective modulators for these receptors. GluD1 receptors encoded by GRID1 appear to act as a mechano-transducer of force between presynaptic terminals and postsynaptic spines, and we are collaborating with Dr. Cheng Zhu at Georgia Tech to evaluate the role of mechanical forces involved in GluD1 function.
Research Topics
Ongoing Studies
We are working on the following topics, which are currently supported by the NIH-NINDS, NIMH, GRIN Therapeutics, the GRIN2B Foundation, in addition to generous donors to the Center for Functional Evaluation of Rare Variants (CFERV)
Novel Subunit-Selective Allosteric Modulators of NMDA Receptor
Functional Effects of Glutamate Receptor Mutations in Human Diseases
Mechanism of Glutamate Receptor Activation
Function of GRID and GluN3 receptors in the CNS
Previously Published Studies
We have previously worked on the multiple topics, and continue to be interested in these areas through multiple collaborations as well as some experimentation.
Functional Roles of Protease Receptors in the Central Nervous System
Allosteric Regulation of Glutamate Receptors by Endogenous Extracellular Ions
Neuroinflammation Controls Microglial Expression of Cell Surface Receptors
Control of Glutamate Receptor Ion Channel Function by Phosphorylation