Thesis Title: Theoretical Investigation of the Structure and Function of Ionotropic Glutamate Receptors.

Graduation Date: 2010

PhD Advisor: Dr Maria Kurnikova

Elevated levels of glutamate during cerebral ischemia play a major role in excitotoxicity of glutamate receptors (GluRs) leading to neuron death and devastating effects on the central nervous system.  Studies show that antagonists of the AMPA GluR subtype have a neuroprotective effect on a variety of ischemic models.  Functional diversity of GluR in the brain is revealed in clinical trials showing antagonists produce such side effects as developmental dysfunction and psychosis.  Clearly understanding the mechanism by which GluRs function is critical for rational drug design which may provide neuroprotection over antagonists of the receptor.  More importantly exploring subtle differences in receptor subtypes provide a means of drug specificity, eliminating potential side effects.  Structural and theoretical (Speranskiy et al. Biochem. 2005 Aug 30;44(34):11508) studies of AMPA receptors indicate that electrostatic interactions play an important role in both ligand attraction to the ligand binding S1-S2 extracellular domain, and interactions at the S1-S2 domain interface.  Modeling the conformational change in S1-S2 that occurs upon ligand binding indicate the ligand bound conformation may be stabilized by hydrogen bonding and long-range electrostatic attraction.  These results contribute to the current working hypothesis that electrostatic interactions play an important role in the glutamate receptor function.  A multiple-methodology is being used to study GluR function using long molecular dynamics trajectories.  Also being conducted is a rigorous Investigation of the interactions between the extracellular domain dimer and surface of the lipid bilayer through Monte Carlo simulations and electrostatic Poisson-Boltzmann theory.


Current location: postdoctoral researcher in the lab of Dr. Dirk Gillespie at Rush University Medical Center in Chicago

1996 - 2000 - B.S. Physics Millersville University, Millersville, PA
2005 - 2010 - PhD Molecular Biophysics Carnegie Mellon University