Afton Widdershins

Investigating the Development and Behavior of Heterogeneous Tumors

Class of 2019


  • Education
    • Bellaire High School, Bellaire Texas, 2015
    • The College of Wooster, BA in Biochemistry and Molecular Biology, 2019
    • The College of Wooster, BA in Mathematics, 2019
  • Professional experience
    • Fred Hutch Cancer Research Center Summer Intern
    • The College of Wooster Biology Department, Teaching Assistant & Peer Tutor
    • The College of Wooster Chorus, Manager
    • Beta Beta Beta – Biology National Honor Society
    • Pi Mu Epsilon – Mathematics Honors Society

IS Thesis Abstract

 Several advancements in cancer treatment center on the idea that mutations in a tumor can be targeted with drugs. However, the presence of intratumor heterogeneity can complicate using targeted therapies as tumors can escape through the presence of an already resistant subclone or through developing resistance. Using a Boolean model of the regulatory network of a mammalian cell, we have constructed a simulation of a cell population, where each cell runs their own instance of said model. Working with the simulation showed that populations will evolve a response to high levels of TRAIL. The model also showed that low mutation rates tend to be more fit than high mutation rates, though the fitness of various mutation rates differs depending on the level of TRAIL stress. These results support the idea that cells susceptible to treatment can outcompete resistant cells given the proper stress conditions.

Figure 1. Modeling the evolution of TRAIL resistance. Cell populations able to accumulate mutations during DNA synthesis or DNA repair can evolve resistance to lethal doses of the apoptosis-inducing TRAIL, maintaining a tumorigenic population in this hostile environment.