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Meredith Stone

Class 2012
Education BS, Cornell University
Email mstone14@jhmi.edu
Mentor

Dr. Steve Baylin

Dr. Cindy Zahnow

Research Interests

Our lab studies cancer epigenetics and is working on developing epigenetic therapy to treat solid tumors. In cancer, DNA methylation increases in gene promoter regions, which can lead to gene silencing and is one way that tumor suppressor genes can be inactivated. Our lab has previously shown that transient, low doses of DNA demethylating agents have durable anti-tumor effects on epithelial tumor cells. Combining epigenetic therapy with conventional therapy has the potential for even greater benefit.

Specifically, my thesis project is to determine if a combination of epigenetic and immune therapies can have an anti-tumor effect on ovarian tumors in immune competent mice. 5-azacytidine, a DNA demethylating agent, has been shown in our lab to upregulate a panel of immune related genes in ovarian cancer cell lines. My hypothesis is that if we can upregulate these immune genes in vivo, immune cells could be recruited to the tumor, where immune therapy could activate the immune cells and lead to tumor death. My first question is whether or not treating just the cancer cells with 5-azacytidine will recruit the immune cells of a syngeneic mouse, and if so will that, in combination with immune therapy, have an antitumorigenic effect. In the future I will look at the effect that treating the mouse with epigenetic therapy before injecting tumor cells has on the immune reaction to the tumor and tumor growth, and finally I will examine how treating both the mouse and the tumor cells post injection affects the immune and tumor response. This final experiment will be a more therapeutically relevant model, which could impact patient treatment.