The major interest of our laboratory is correlating the structure and function for membrane protein receptors and channels, primarily neuroreceptors. Utilizing recent biotechnological advances, we are reexamining overexpressed recombinant human glycine receptors. This receptor is part of a superfamily of ligand-gated ion channels critical in transmission of synaptic signals. Recently, we have used circular dichroism, and mass spectrometry coupled with chemical modification to more critically examine the topology of this paradigmatic ion channel. We are also engaged in studies examining the of lipid composition on the structure and function of the glycine receptor. In order to continue to characterize the structure of this ion channel we are systematically incorporating cysteine residues at select regions of the receptor and incorporating non-specific crosslinking and cleavage reagents (to map accessibility and proximity); and spin labels (in collaboration with Dr. Sunil Saxena, Dept. of Chemistry);. Computational modeling studies of the glycine receptor are also being conducted in collaboration with with Dr. Rob Coalson (Dept. of Chemistry); and Dr. Maria Kurnikova (Carnegie Mellon University);. Crystallographic trials are being conducted in collaboration with Dr. R.O. Fox (University of Texas Medical Branch at Galveston);. We have also recently begun characterizing cellular elements that bind the receptor and may be important in receptor clustering, synaptogenesis, and cross-talk with other membrane proteins. In addition to these studies, we have also recently initiated studies on neurodegenerative disorders. In order to examine the effect of oxidative stress on dopaminergic neurons in Parkinson’s disease we are collaborating with Dr. Terri Hastings (Dept. of Neurology); to identify proteins that may be selectively modified by dopamine under oxidative conditions. We are using 2D gel electrophoresis coupled with mass spectrometry to identify mitochondrial and cellular proteins whose cysteinyl residues become oxidized under oxidative stress or in model Parkinson’s systems. We have also recently begun investigations aimed at examining amyloidogenesis in Alzheimer’s disease. Amongst its many natural targets, neprilysin, a Zn-dependent protease, has been shown to cleave fibril-forming ABeta peptide both in vitro and in vivo. By engineering the active site of this enzyme, we propose to create an ABeta-selective protease that may be used in combating Alzheimer’s disease. These studies are being conducted in collaboration with Dr. Marc Glucksman (Rosalind Franklin Medical School); and Dr. Joseph Glorioso (Dept. Of Molecular Genetics and Biochemistry);.  Research projects are discussed in detail on our group website.