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Clodagh O’Shea, PhD
Exploiting Viruses to Understand and Treat Cancer
Associate Professor, Molecular and Cell Biology Laboratory; William Scandling Developmental Chair, The Salk Institute
2 Riverside Circle, Roanoke, VA 24016
Clodagh O’Shea’s research blends cancer biology, virology, structural biology, imaging, synthetic biology, and genomics to identify critical growth regulatory mechanisms and develop novel therapies. This has led to contributions in different fields, revealing RNA export as the therapeutic target for oncolytic viral therapy, a novel heterochromatin silencing mechanism that inactivates p53 and a structural basis through which small viral oncoproteins ‘win’ and disrupt disparate tumor suppressor hubs. Recent work from her laboratory has revealed that DNA breaks at viral and cellular genomes are not weighted equally and activate distinct signaling responses. At small viral genomes, ATM signaling is not amplified by H2AX across megabases of chromatin. Thus, gH2AX foci discriminate ‘self’ and ‘non-self’ genomes and provide an elegant mechanism to neutralize viral replication without jeopardizing cellular viability. This has important implications for pathological conditions where DNA damage is common, such as cancer and aging. Her lab has also developed new technologies to address critical challenges in basic biology and therapy, including new imaging approaches that enable 3D chromatin ultrastructure to be visualized at nucleosome resolutions and megabase scales. In addition, Dr. O'Shea will discuss synthetic virology that exploits modular genome assembly to create designer viruses that specifically seek and destroy tumor cells.