PhD Thesis
Discover the novel research behind April's PhD thesis, exploring immunogenic cell death and its impact on advancing cancer immunotherapy.
Mechanisms of Immunogenic Cell Death in Tumor Cells Infected with Oncolytic Vaccinia Virus
Thesis title
April’s research explored how oncolytic vaccinia viruses (oVACVs) kill cancer cells while triggering immune responses against tumours, a process known as immunogenic cell death. Her work focused on characterising the unique ways oVACVs induce cell death and how both viral and tumour cell genetics influence this process.
Her thesis features a comprehensive literature review and a detailed analytical report based on her three complementary research projects.
Understanding Immunogenic Cell Death in Cancer Virotherapy
April discovered that oVACVs cause lytic cell death in various cancer cell lines, but they suppress many programmed cell death pathways before lysis. While classical forms of cell death like necroptosis and apoptosis were not activated, evidence of alternative pathways, such as gasdermin E-mediated pyroptosis, was identified in certain cases.
Improving Oncolytic Virotherapy in Cancer Treatment
April investigated two specific vaccinia virus genes, one previously undescribed, which act as inhibitors of inflammatory cell death. By removing these genes from the viral genome, she demonstrated an increase in cancer cell lysis, revealing potential strategies to enhance oVACV’s effectiveness.
Combinational Approaches to Enhance Virotherapy
April's work highlighted the role of tumour cell genetics in sensitivity to oncolytic therapies. She found that tumour cells with BRCA2 mutations were more vulnerable to oVACV-induced death and identified potential benefits of combining oVACV therapy with inhibitors targeting DNA repair proteins, such as PARP1 and DNA-PKcs, to improve therapeutic outcomes.
Thesis Defence and Review
April successfully defended her PhD thesis in her viva examination in September 2024. Her work received high praise from her examiners, Professor Stephen Tait and Dr. Valeria Lulla, who described the thesis as:
⭐️⭐️⭐️⭐️⭐️
"An excellent thesis."
"An important and substantial piece of work."
"A great pleasure to read."
This recognition reflects April’s dedication to producing impactful and meticulously crafted research.