Barry Wolfe, PhD
Professor Department of Pharmacology
Georgetown University Medical Center
C402 Med-Dent Building, Box 571443
3900 Reservoir Road, NW
Washington, DC 20057-1455
Phone: 202 687-1420
bwolfe01@georgetown.edu
http://pharmacology.georgetown.edu/faculty/facwolfe.html
Research Interests
Regulation of neurotransmitter receptors and response
Research Summary
Neurotransmitter receptors are involved in transducing information in the central nervous systems. My laboratory studies these receptors and their associated biochemical signalling systems. One line of investigation currently underway involves the study of receptors for the neurotransmitter glutamate, which is the major excitatory neurotransmitter in the central nervous system and is vital to many physiological functions, including learning and memory. It is also important in several pathological states, such as spinal cord injury and Alzheimer’s disease. There are multiple types of glutamate receptors; metabotropic receptors coupled to enzymes; and ionotropic receptors that are ligand-gated ion channels. The cDNAs encoding several subunits of one type of ionotropic glutamate receptor called the NMDA receptor have been cloned and the proteins expressed. Using molecular biological techniques, selective polyclonal and monoclonal antibodies to each subunit have been generated in the laboratory. The goal of these studies is to generate selective probes to study the regulation of receptor expression by genetic and epigenetic mechanisms. Questions relating to the stoichiometry of the multi-subunit composition of the NMDA receptor as well as post-translational modifications of the receptors that may alter their functionality are being addressed. These reagents are also being used to examine the regulation of these signaling proteins to the ability of aged rats to learn and remember and to examine the possibility that these proteins are involved in the mechanisms of cell death accompanying spinal cord injury.
Representative Publications
- Adams MM, Smith TD, Moga D, Gallagher M, Wang Y, Wolfe BB, Rapp PR, Morrison JH.: Hippocampal dependent learning ability correlates with N-methyl-D-aspartate (NMDA) receptor levels in CA3 neurons of young and aged rats. J Comp Neurol. 432:230-243, 2001
- Yeh JJ, Yasuda RP, Davila-Garcia MI, Xiao Y, Ebert S, Gupta T, Kellar KJ, Wolfe BB.: Neuronal nicotinic acetylcholine receptor alpha3 subunit protein in rat brain and sympathetic ganglion measured using a subunit-specific antibody: regional and ontogenic expression. J Neurochem. 77:336-346, 2001
- Al-Hallaq RA, Yasuda RP, Wolfe BB. Enrichment of N-methyl-D-aspartate NR1 splice variants and synaptic proteins in rat postsynaptic densities. J Neurochem. 77:110-119, 2001
- Yeh JJ, Ferreira, M, Ebert S, Yasuda RP, Kellar KJ, Wolfe BB: Axotomy and nerve growth factor regulate levels of neuronal nicotinic acetylcholine receptor alpha3 subunit protein in the rat superior cervical ganglion. J Neurochem. 79:258-265, 2001
- Brown KM, Wrathall JR, Yasuda RP, Wolfe BB: Quantitative measurement of glutamate receptor subunit expression in the postnatal rat spinal cord. Dev. Brain Res. 137: 127-133, 2002
- Al-Hallaq RA, Jarabek BR, Fu Z, Vicini S, Wolfe BB, Yasuda RP. Association of NR3A with the N-Methyl-D-aspartate Receptor NR1 and NR2 Subunits. Mol Pharmacol. 62:1119-1127, 2002