Ian Zonfa

Boolean Modeling of the Interactions Between Inflammation, Hypoxia, and the Epithelial-Mesenchymal Transition (EMT)

Class of 2022


  • Education
    • Brecksville-Broadview Heights High School, Broadview Heights, OH, 2018
    • The College of Wooster, BA in Biochemistry and Molecular Biology, 2022
    • The College of Wooster, Minor in Political Science, 2022
  • Professional experience
    • Health Coach -Wooster Community Hospital
    • Honors-Dean’s Scholarship, Dean’s List Spring 2019, Fall 2019, Spring 2021, and Fall 2021
    • Camp Ho Mita Koda, Summer Camp Counselor, Clinic Assistant
    • The College of Wooster, Office of Residence Life, Resident Assistant
    • The College of Wooster, Department of Chemistry, Teaching Assistant

IS Thesis Abstract

Despite the COVID-19 pandemic, cancer has remained the second largest cause of death in the U.S. Cancer is a broad group of diseases where tumor cells can divide rapidly, create more tumor cells in a “tumor microenvironment”, and often metastasize. Cancer cell behaviors are usually classified into hallmarks, with six primary hallmarks, and multiple secondary ones. One of these secondary hallmarks is inflammation, which helps create a tumor microenvironment that recruits blood vessels to help spread the tumor. One key hallmark that aids this spread is the Epithelial-Mesenchymal Transition (EMT), where epithelial cells transition into migratory cells and spread. The inflammatory cytokines IL-6 and TGF-β provide several links between EMT, cancer, and inflammation. We sought to model these interactions to show that inflammation can drive EMT. Our model also links TGF-β signaling to hypoxia, or an absence of oxygen. After testing an epithelial cell pushed to a hybrid EMT state by its strong growth factor and monolayer breakage environment, we found that IL-6 signaling causes a transient mesenchymal state in both normoxic and hypoxic conditions. It was also found that TGF-β caused our hybrid E/M cell to commit to full EMT, but only in hypoxia. As a result, our model predicted links between inflammatory signaling, hypoxia, and EMT, which can now be tested in vitro.

Figure 1. The autocrine feedback loops responsible for locking in the Epithelial to Mesenchymal Transition
Figure 2. Ian presenting his work at IS Symposium, 2022

Webpage: https://www.linkedin.com/in/ian-zonfa-180363225