The O'Shea Lab's research focuses on three main areas:
1) Identifying the cellular targets and pathways driving deregulation of cell growth
Tumors contain many different mutations, making it hard to identify which have a critical role in uncontrolled cell growth and would make the best therapeutic targets. Adenovirus, on the other hand, achieves the same sort of growth using only a small number of proteins. Dr. O’Shea is working to reveal which cellular elements the virus is targeting, with the goal of identifying key pathways leading to deregulated cell growth. Her lab is currently exploring the p53 tumor suppressor pathway, PI-3 Kinase/mTOR signaling and RNA export/processing in tumorigenesis.
2) Working out the program responsible for deregulated cell growth and finding therapies to disconnect it
The O’Shea lab is also using adenovirus infection to reveal the larger scale program that allows pathological cell growth to occur. Tumor mutations do not act in isolation, but within complex cellular networks; therapies that aim at a combination of targets will surely be necessary in order to deactivate this program. They are taking a systems biology approach that will determine the shared molecular signatures of cells infected with adenovirus and tumor cells. This will also allow them to test combination therapies capable of blocking aberrant cell growth, while leaving healthy cells untouched.
3) Manipulating viruses as novel agents for cancer treatment, capable of killing tumor cells, specifically, from inside
Dr. O’Shea is especially interested in using viruses to kill cancer cells, something called oncolytic viral therapy. By creating defective viruses that are unable to bypass the limitations on growth found in normal cells, she can create viruses that will selectively replicate only in tumor cells, where, due to mutations, these limitations don’t exist.