Dr. Wolfe is not available as a PhD thesis mentor but is available as a co-mentor or thesis committee member or a mentor for MS projects.
Current Research: Recent projects have focused on the metabotropic glutamate receptor 1 (mGlu1 R). mGlu1 R are normally expressed in neurons, most highly in the cerebellum. However, in collaboration with other researchers in our Department, we have found that the mGlu1 R is an oncogene and is ectopically expressed in many cancers. The cancer cells, when they over-express the mGlu1 R, become dependent or 'addicted' to the stimulation via this receptor. Recent graduate students have shown that blocking this receptor, or silencing its gene, results in dramatic decreases in the rate of growth of tumors. Current and future experiments will focus on discovering the mechanism(s) by which this receptor stimulates cancer cell growth as well as the development of high-throughput assays to screen for drugs that negatively regulate this receptor.
Current projects: These future projects will be carried out by Dr. Carrie Bowman Dalley, Dr. Barbara Wroblewska, and myself. Past studies in the lab have established mGlu1 R as an oncogene. Although the canonical signaling pathway for this receptor is via Gq stimulation of PLC causing increases in IP3 and Ca++, the signaling pathway for stimulation of cancer cell growth seems to be distinct and, instead, involves interaction of the agonist-bound mGlu1 R with beta-arrestin, internalization of the receptor causing stimulation of (unknown) enzymatic pathways. Our future projects will identify the signaling pathways and explore novel hypotheses as to how this receptor works.
- Dalley CB, Wroblewska B, Wolfe BB, Wroblewski JT The Role of Metabotropic Glutamate Receptor 1 Dependent Signaling in Glioma Viability. J Pharmacol Exp Ther 367:59-70, 2018.
- DeDominicis KE, Sahibzada N, Olson TT, Xiao Y, Wolfe BB, Kellar KJ and Yasuda RP The stoichiometry (α4)3(β2)2 of the nicotinic acetylcholine receptor predominates in the rat motor cortex. Molecular Pharmacology July 11, 2017.
- Gelb T, Pshenichkin S, Hathaway HA, Grajkowska E, Dalley CB, Wolfe BB, Wroblewski JT. Atypical signaling of metabotropic glutamate receptor 1 in human melanoma cells. Biochem Pharmacol. doi:10.1016/j.bcp.2015.08.091, 2015.
- Tuan EW, Horti AG, Olson TT, Gao Y, Stockmeier CA, Al-Muhtasib N, Bowman Dalley C, Lewin AE,Wolfe BB, Sahibzada N, Xiao Y, Kellar KJ. AT-1001 Is a Partial Agonist with High Affinity and Selectivity at Human and Rat α3β4 Nicotinic Cholinergic Receptors. Mol Pharmacol. 88(4), 640-649, 2015.
- DiRaddo JO, Miller EJ, Bowman-Dalley C, Wroblewska B, Javidnia M, Grajkowska E, Wolfe BB, Liotta DC, Wroblewski JT. Chloride is an Agonist of Group II and III Metabotropic Glutamate Receptors. Mol Pharmacol. 88(3), 450-459, 2015.
- Hathaway HA, Pshenichkin S, Grajkowska E, Gelb T, Emery AC, Wolfe BB, Wroblewski JT. Pharmacological characterization of mGlu1 receptors in cerebellar granule cells reveals biased agonism. Neuropharmacology 93:199-208, 2015
- Gelb T, Pshenichkin S, Rodriguez O, Hathaway HA, Grajkowska E, DiRaddo JO, Wroblewska B, Yasuda R, Albanese C, Wolfe BB, Wroblewski JT. Metabotropic Glutamate Receptor 1 acts as a Dependence Receptor Creating a Requirement for Glutamate to Sustain the Viability and Growth of Human Melanomas. Oncogene, 34:2711-20, 2015
- Ullrich L, Dumanis SB, Evans TM, Jeannotte AM, Leonard C, Rozzi SJ, Taylor CM, Gale K, Kanwal JS, Maguire-Zeiss KA, Wolfe BB, Forcelli PA. From student to steward: the Interdisciplinary Program in Neuroscience at Georgetown University as a case study in professional development during doctoral training. Med Educ Online 19:22623, 2014
- Diraddo JO, Miller EJ, Hathaway HA, Grajkowska E, Wroblewska B, Wolfe BB, Liotta DC, Wroblewski JT: A Real-Time Method for Measuring cAMP Production Modulated by Gαi/o-Coupled Metabotropic Glutamate Receptors. J Pharmacol Exp Ther. 2014 Jun;349(3):373-82
- Hussmann GP, Dedominicis KE, Turner JR, Yasuda RP, Klehm J, Forcelli PA, Xiao Y, Richardson JR, Sahibzada N, Wolfe BB, Lindstrom J, Blendy JA, Kellar KJ: Chronic sazetidine-A maintains anxiolytic effects and slower weight gain following chronic nicotine without maintaining increased density of nicotinic receptors in rodent brain. J Neurochem. 2014 May;129(4):721-31
- Hussmann GP, TurnerJR, Lomazzo E, Venkatesh R, Cousins V, Xiao Y, Yasuda RP, Wolfe BB, Perry DC, Rezvani AH, Levin ED, Blendy JA, Kellar KJ: Chronic sazetidine-A at behaviorally active doses does not increase nicotinic cholinergic receptors in rodent brain. J Pharmacol Exp Ther 343:441-450, 2012
- Emery AC, Diraddo JO, Miller E, Hathaway HA, Pshenichkin S, Takoudjou GR, Grajkowska E, Yasuda RP, Wolfe BB, Wroblewski JT. Ligand Bias at Metabotropic Glutamate 1a Receptor: Molecular Determinants that Distinguish beta-arrestin from G Protein Mediated Signaling. Mol Pharmacol. May 14, 2012
- Hussmann GP, Yasuda RP, Wolfe BB, Xiao, Y, Kellar KJ Endogenously expressed muscarinic receptors in HEK293 cells augment up-regulation of stably expressed alpha4-beta2 nicotinic receptors. J Biol. Chem. 286:39726, 2011
- Lomazzo E, Hussmann GP, Wolfe BB, Yasuda RP, Perry DC, Kellar KJ Effects of chronic nicotine on heteromeric neuronal nicotinic receptors expressed in rat primary cultured neurons. J Neurochem. 119:153-164, 2011
- Lomazzo E, MacArthur L, Yasuda RP, Wolfe BB, Kellar KJ: Quantitative analysis of the heteromeric neuronal nicotinic receptors in the rat hippocampus. J Neurochem 115: 625-634, 2010
- Emery AC, Pshenichkin S, Takoudjou GR, Grajkowski E, Wolfe BB, Wroblewski JT: The protective signaling of metabotropic glutamate receptor 1 is mediated by sustained, beta-arrestin-1-dependent ERK phosphorylation. J Biol Chem 285: 26041-26048, 2010
- Mao D, Perry DC, Yasuda RP, Wolfe BB, Kellar KJ.: The alpha4beta2alpha5 nicotinic cholinergic receptor in rat brain is resistant to up-regulation by nicotine in vivo. J Neurochem. 104:446-56, 2008
- Ortinski PI, Turner JR, Barberis A, Motamedi G, Yasuda RP, Wolfe BB, Kellar KJ, Vicini S.: Deletion of the GABA(A) receptor alpha1 subunit increases tonic GABA(A) receptor current: a role for GABA uptake transporters. J Neurosci. 26:9323, 2006
- Lu C, Fu Z, Karavanov I, Yasuda RP, Wolfe BB, Buonanno A, Vicini S.: NMDA receptor subtypes at autaptic synapses of cerebellar granule neurons. J Neurophysiol. 96:2282-94, 2006
- Mao D, Yasuda RP, Fan H, Wolfe BB, Kellar KJ.: Heterogeneity of nicotinic cholinergic receptors in rat superior cervical and nodose Ganglia. Mol Pharmacol. 70:1693-9, 2006
- Marritt AM, Cox BC, Yasuda RP, McIntosh JM, Xiao Y, Wolfe BB, Kellar KJ.: Nicotinic cholinergic receptors in the rat retina: simple and mixed heteromeric subtypes. Mol Pharmacol. 68:1656-1668, 2005
- Brown KM, Wolfe BB, Wrathall JR.: Rapid functional recovery after spinal cord injury in young rats. J Neurotrauma. 22:559-574, 2005
- Brown KM, Wrathall JR, Yasuda RP, Wolfe BB.: Glutamate receptor subunit expression after spinal cord injury in young rats. Brain Res Dev Brain Res. 152:61-68, 2004
- Jarabek BR, Yasuda RP, Wolfe BB.: Regulation of proteins affecting NMDA receptor-induced excitotoxicity in a Huntington's mouse model. Brain 127: 505-516, 2004
- Carter TL, Rissman RA, Mishizen-Eberz AJ, Wolfe BB, Hamilton RL, Gandy S, Armstrong DM.: Differential preservation of AMPA receptor subunits in the hippocampi of Alzheimer's disease patients according to Braak stage. Experimental Neurology, 187:299-309, 2004
- Mishizen-Eberz AJ, Rissman RA, Carter TL, Ikonomovic MD, Wolfe BB, Armstrong DM.: Biochemical and molecular studies of NMDA receptor subunits NR1/2A/2B in hippocampal subregions throughout progression of Alzheimer's disease pathology. Neurobiol Dis 15: 80-92, 2004
- Rissman RA, Mishizen-Eberz AJ, Carter TL, Wolfe BB, De Blas AL, Miralles CP, Ikonomovic MD, Armstrong DM.: Biochemical analysis of GABA(A) receptor subunits alpha 1, alpha 5, beta 1, beta 2 in the hippocampus of patients with Alzheimer's disease neuropathology. Neurosci 120:695-704,2003
- 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
- Brown KM, Wrathall JR, Yasuda RP, Wolfe BB.: Quantitative measurement of glutamate receptor subunit protein expression in the postnatal rat spinal cord. Dev Brain Res 137: 127-133, 2002
- Yeh J, 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
- 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, Yasuda RP, Dávila-García 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
- 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
- Prybylowski KL, Grossman SD, Wrathall JR, Wolfe BB.: Expression of splice variants of the NR1 subunit of the N-methyl-D-aspartate receptor in the normal and injured rat spinal cord. J Neurochem 76:797-805, 2001
- Prybylowski KL, Wolfe BB.: Developmental differences in alternative splicing of the NR1 protein in rat cortex and cerebellum. Dev Brain Res 123:143-150, 2000
- Wang Y, TesFaye E, Yasuda RP, Mash DC, Armstrong DM, Wolfe BB.: Effects of post-mortem delay on subunits of ionotropic glutamate receptors in human brain. Mol Brain Res 80:123-131, 2000
- Prybylowski K, Rumbaugh G, Wolfe BB, Vicini S.: Increased exon 5 expression alters extrasynaptic NMDA receptors in cerebellar neurons. J Neurochem 75:1140-1146, 2000
- Grossman SD, Wolfe BB, Yasuda RP, Wrathall JR.: Changes in NMDA receptor subunit expression in response to contusive spinal cord injury. J Neurochem 75:174-184, 2000
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