Funding outcome

Epithelial ovarian cancer (EOC) is one of the leading causes of death related to gynecologic cancers. Current treatments against advanced EOC are ineffective, highlighting an urgent need for novel treatments. Research in Dr. Fu's lab has determined that an enzyme called NSUN2, which modifies RNA molecules in the cell, has a tumor-promoting role in EOC and is correlated with reduced survival in ovarian cancer patients when it is present at high levels. We have found that while reducing NSUN2 levels slows the growth of EOC cells, the cells have adaptive mechanisms to overcome this effect over time. We suspect that the adaptive mechanism involves other genes that step in to help when there is not enough NSUN2. To figure out what the partner genes are, we used a computer analysis to find some potential suspects. Of the potential partners that came up, the strongest result led to a protein called NHP2. We hypothesize that simultaneous deactivation of NSUN2 and NHP2 could have even greater effects on cancer cell growth than just NSUN2 alone. To test this, we will analyze how well EOC cells grow when their NSUN2 and NHP2 are deactivated compared to when NSUN2 is deactivated alone. The experiments we will use to accomplish this are different assays that test the speed of cell growth, how well cells can survive, and how often cells are dying. If we obtain the expected results, we will take it one step further and test our hypothesis using mouse models to analyze the rate of tumor growth in a living organism. If we do not obtain the expected results of NHP2 being the partner of NSUN2, we will use the same strategies to test the other genes that came up as potential partners. Success in our research findings could redefine ovarian cancer treatment strategies and provide a potential treatment option for patients with advanced EOC, which are currently limited.