Dr Clodagh O'Shea obtained her Bachelor's degree in Biochemistry from the University College Cork, where she was honored with the Graduate of the Year and Peel Memorial Prizes. She pursued her graduate studies in Dr Mike Owen's laboratory as a bursar at the Imperial Cancer Research Fund in London. In 1997, she obtained her PhD for her research in mouse models that established both a critical role for the surface expression of the pre-T-cell receptor in early thymocyte development, as well as Raf kinase signaling for T-cell-positive selection. Following work with Raleigh International in Namibia, Dr O'Shea's interest in translational therapies led her to pursue postdoctoral studies in Dr Frank McCormick's laboratory at the UCSF Cancer Center as a Human Frontiers in Science Program Fellow. Subsequently, she was awarded a Leukemia Society of America Fellowship to continue her postdoctoral research on genetically modified viruses that selectively destroy tumor cells. In 2003, together with co-investigators Dr Frank McCormick and Dr Michael Korn, she received a University of California Discovery grant – one of the largest ever awarded for a biomedical project – to research on novel oncolytic viral strategies. Dr O'Shea's work revealed that late viral RNA export, rather than p53 inactivation, is the major determinant of ONYX-015 selectivity, an oncolytic virus that shows promise as a cancer therapy. These studies uncovered tumor cell differences in RNA export as a previously unidentified and therapeutically exploitable target. In clinical trials, many patients' tumors were found to be resistant to ONYX-015 therapy. Dr O'Shea found that heat shock, induced by febrile temperatures or drugs, rescues viral RNA export and sensitizes resistant tumor cells to ONYX-015 therapy, which has important clinical applications. Dr O'Shea has also been using viral proteins as tools with which to uncover critical cellular targets that may also be deregulated in tumor cells. Recently, she found that adenovirus encodes two viral proteins that bypass a nutrient/growth factor checkpoint for mTOR activation and protein translation, an emerging and important tumor target. She was acknowledged for this work as an Upstate Young Cell Signaler Award Finalist. Dr O'Shea's current research focuses on exploiting adenovirus as a system in which to discover how the pleiotropic perturbation of pivotal growth regulatory pathways are integrated in complex cellular networks to elicit aberrant replication, and how to uncouple them. She is using this knowledge to inform the design of rational combination drug therapies and replication-competent viruses for the treatment of cancer.
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