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Current Research:
High-grade astrocytomas, specifically WHO grade IV glioblastoma multiforme (GBM) are the most common primary malignant brain tumor in adults. Despite the current standard of care (resection, chemotherapy, and radiation), GBM confers a poor prognosis with a median survival rate that has increased only by months in the past several decades. Hence, there is a great need for novel therapies that target GBM cells while leaving normal brain tissue unharmed. One such proposed target is the EphA2 receptor, which our laboratory has shown to be overexpressed in GBM tumors and cell lines, and nearly absent in normal tissue. Activation of EphA2 by its ligand, ephrinA1, induces phosphorylation and degradation of the EphA2 protein, and subsequently leads to decreased tumorigenic properties such as invasion, migration, and anchorage independent growth.
Until recently, ephrinA1 was believed to be able to activate EphA2 only when in a dimeric or oligomeric state, or when anchored to the membrane of an adjacent cell. However, we have recently reported that a monomeric form of ephrinA1 is released into the media of ephrinA1-transfected U-251 (GBM cell line) cells and that it can act in a paracrine fashion as a soluble monomer and functional ligand for EphA2. Monomeric ephrinA1 causes receptor phosphorylation and downregulation, and decreases the invasiveness and migration of carcinogenic cells. While tumor-suppressing abilities of monomeric ephrinA1 have been established, not much is currently known about the mechanism of release of ephrinA1 from the cell membrane, or the downstream signalling pathways stimulated by its binding to EphA2. My project encompasses understanding the mechanism of ephrinA1 cleavage from the cell membrane, downstream signalling as a result of monomeric ephrinA1 activation of the EphA2 receptor, and potential cytotoxin therapies using the monomeric ephrinA1 ligand to target EphA2-overexpressing GBM cells.
Honors and Awards:
Posters Presentations:
Amanda Beauchamp, Christopher Turner. “Postnatal Brain Injury as a Model for Schizophrenia: Possible Relationship between NMDAR blockade and Changes in Dopamine Synthesis.” SROP Poster Session, Wake Forest University. Winston-Salem, NC 2006.
Amanda Beauchamp, Christoper Turner. “Neonatal Brain Injury and Expression of Synaptic Proteins: SNAP25.” SROP Poster Session, Wake Forest University. Winston-Salem, NC 2005.
Amanda Beauchamp, Denise M. Gibo, Jill Wykosky, Peter Dickinson, and Waldemar Debinski. “The Presence of Ephs and ephrins in Canine Brain Tumors.” Eph/ephrins and Cancer Conference, Winston-Salem, NC 2008
Publications:
Lema Tome CM, Nottingham CU, Smith CM, Beauchamp AS, Leung PW, Turner CP. Neonatal exposure to MK801 induces structural reorganization of the central nervous system. Neuroreport. 2006 May 29;17(8):779-83. |