Robert E. Oswald
Professor

Phone

607-253-3877
607-253-3659(fax)

Address

Department of Molecular Medicine
C3 167 Veterinary Medical Center
College of Veterinary Medicine
Cornell University
Ithaca, NY 14853-2703

Email

Web Sites

Lab Web Site
Department Profile

Background

• Ph.D. in Biochemistry, Vanderbilt University
• Molecular Neurobiology, Pasteur Institute
  
• Guggenheim Fellowship, Harvard University/Cornell University
  
• Fulbright Fellowship, University of Oxford
• Alfred P. Sloan Fellow, Cornell University
• Harold S. Vanderbilt Scholar, Vanderbilt University
  

Research Description

Our research interests center on the structure and function of proteins involved in signal transduction. These include two important membrane proteins (nicotinic acetylcholine receptors and glutamate receptors) and an intracellular GTP binding protein (Cdc42Hs). Nicotinic acetylcholine and glutamate receptors are large membrane-bound proteins which mediate the flow of ions from the exterior to the interior of a cell following an interaction with a small organic molecule (i.e.,an agonist). Acetylcholine receptors are important neurotransmitter receptors in skeletal muscle, the peripheral nervous system, and the central nervous system; glutamate receptors are the primary excitatory neurotransmitter receptors in the vertebrate central nervous system. Cdc42Hs is a soluble protein involved in signaling pathways related to the structure of cytoskeleton.

Nicotinic acetylcholine receptors: Nicotinic acetylcholine receptors are found in electroplaque, skeletal muscle and nerve cells and translate the binding of acetylcholine into the flow of ions across the cell membrane. We are interested in both the nicotinic acetylcholine receptors found in electroplaque/skeletal muscle and the central nervous system. Current studies involve using a combination of specifically designed agonists and antagonists and site-directed mutagenesis of the protein to study the amino acids important for activation and ion flux.

Glutamate receptors: The kainate receptor, a subtype of glutamate receptors, is present in many neurons and is an important neurotransmitter receptor. Several have been cloned in our laboratory and analysis of the glycosylation sites established a new model for the transmembrane topology of these receptors. Current efforts are directed at molecular modeling of these receptors and the use of site-directed mutagenesis to help define the important regions of the binding interface. In addition, NMR spectroscopy is binding used to determine the three dimensional structure of several isolated domains of glutamate receptors.. Because of its high concentration in brain and its importance in neuronal excitability, further characterization of this receptor will be of considerable importance to the understanding of epilepsy and neuronal death.

Cdc42Hs and related proteins: GTP binding proteins regulate a wide variety of processes in all living cells. One subtype of this large class of receptors, the rho family of ras-like proteins, seems to be involved in cytoskeletal organization and the mutations in proteins in regulatory pathways in which they function can lead to cell transformation. We are studying the one of these GTP binding proteins, Cdc42Hs, and several of the proteins with which it interacts. We have determined the structure of this protein using heteronuclear, multidimensional NMR spectroscopy and are now focusing on the structure of proteins which regulate Cdc42Hs and the molecular characterization of the binding interfaces.

Publications

A.H. Ahmed, A.P. Loh, D.E. Jane, and R.E. Oswald. Dynamics of the S1S2 glutamate binding domain of GluR2 measured using 19F NMR spectroscopy. J. Biol. Chem. 282: 12773-12784 (2007).

B.G. Kornreich, L. Niu, M.S. Roberson, and R.E. Oswald. Identification of C-terminal domain residues in protein kinase A-mediated potentiation of GluR6. Neuroscience 146: 1158-1168 (2007).

R.E. Oswald, A. Ahmed, M. Fenwick, and A.P. Loh. Structure of glutamate receptors. Current Drug Targets 8: 573-582 (2007).

O.R. Pagan, K. Sivaprakasam, and R.E. Oswald. Molecular properties of local anesthetics as predictors of affinity for nicotinic acetylcholine receptors. J. Neurosci. Res. DOI: 10.1002/jnr.21402 (2007).

R.E. Oswald and A. Ahmed. The relationship between structure and function in the ionotropic glutamate receptor family. In: H. Arias, ed., Biophysical Aspects of Ligand-Gated Ion Channel Receptor Superfamilies, Research Signpost, Kerala pp. 241-258 (2006).

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