James Bundred

Does the temporal order of driver gene mutation affect colonic stem cell phenotype?

As a DPhil student in Professor Simon Buczacki’s lab, my research explores the heretical idea that the temporal order in which cancer driver genes are mutated during colorectal cancer evolution significantly influences the resulting cancer phenotype. Using a combination of wet lab and bioinformatics approaches, I aim to uncover how these mutations affect cancer behaviour and therapy response over time.

In the lab, we leverage advanced gene-editing techniques and colon organoid models, or "mini colons," to replicate early stages of colon cancer. By controlling the sequence of driver gene mutations, we can observe their impact on the biological characteristics of these organoids, providing insights into tumour evolution and potential therapeutic vulnerabilities.

In parallel with this experimental work, I will integrate multi-omics data from large-scale sequencing studies that track the colorectal adenoma-carcinoma transition. This data-driven approach will help us better understand how the temporal dynamics of mutation ordering can inform personalized treatment strategies and improve outcomes for patients.

How could your research ultimately benefit patients?

Current cancer treatments often show highly variable effectiveness, even among patients whose tumours share similar genetic profiles. The reasons for these differences in treatment response remain poorly understood. By investigating how the order of driver gene mutations affect cancer behaviour, my research could help unravel some of this complexity. A deeper understanding of mutational order’s role in therapy resistance or sensitivity could lead to more personalized and effective treatment plans, tailored to the unique evolutionary path of each patient’s cancer.

Additionally, insights into the early stages of colorectal cancer evolution hold significant implications for cancer prevention and screening. By identifying key mutation patterns in the adenoma-carcinoma transition, this research may contribute to more precise risk stratification, helping to refine screening protocols and preventive strategies to catch and manage colorectal cancer earlier, ultimately improving patient outcomes.

About James

I completed my medical degree at the University of Birmingham, where I also achieved a first-class intercalated degree in Biomedical Sciences. During this time, I conducted research on the role of a tumour oxygenase enzyme in driving colon cancer growth and metastasis. Following medical school, I worked as an Academic Foundation doctor at Leeds Teaching Hospitals, spending four months under the guidance of Professor Phil Quirke. There, my research focused on colonic stem cell dynamics and the fixation of driver gene mutations in non-cancerous human colon tissue.

 My interest in early colorectal cancer evolution led to an Academic Clinical Fellowship in General Surgery at the University of Oxford under the supervision of Professor Simon Buczacki. In this role, I studied the epigenetic mechanisms that underpin the early stages of colon cancer evolution, further shaping my current research focus, alongside completing my core surgical training in the Thames Valley region.