Funded by the Dr Elman Poole Research Fellowship
This research focuses on understanding how certain types of cells in the colon (large bowel)
contribute to cancer growth and finding ways to stop it. The colon has a layer of cells called
epithelial cells, which are organized into tiny glandular structures called crypts. Some of these
cells, known as colorectal stem cells (CSCs), normally divide in a controlled way to maintain a
healthy colon. But in cancer, they grow uncontrollably and create tumour cells. Unfortunately,
these cells can adapt and become resistant to treatments.
The research also examines fibroblasts—cells that sit beneath the epithelial cells and send
signals to them. Tumours with more fibroblasts tend to grow faster and are harder to treat. The
goal is to understand how fibroblasts and epithelial cells “talk” to each other and how this
interaction fuels cancer growth. This knowledge could lead to new treatments.
This research project uses advanced techniques, including lab-grown mini-organs (organoids)
that mimic real colon tissue. These organoids are genetically modified to represent different
types of colon cancer. By growing them alongside fibroblasts in a lab, I have observed how
fibroblasts help cancer stem cells grow. Cutting-edge tools like single-cell RNA sequencing and
protein analysis have revealed details about the cells’ behaviour and the substances they
exchange.
Key Achievements
1. Lab-Grown Mini-Organs: I have created organoids with key genetic changes linked to
colon cancer, such as mutations in the APC and TP53 genes.
2. Simulating Cell Interactions: Fibroblasts and organoids were grown together, showing
how fibroblasts boost the growth of cancer stem cells.
3. Detailed Cell Analysis: Advanced molecular techniques have identified specific cell
types and proteins involved in these interactions, highlighting potential drug targets.
Future Plans
1. Develop tools to track and analyse specific cell types in the colon.
2. Test whether changes in fibroblasts can weaken their harmful effects on epithelial cells.
3. Investigate whether the influence of fibroblasts on cancer cells lasts even after they’re
separated.
4. Explore how the order of genetic mutations in cancer cells affects their interaction with
fibroblasts.
Why It Matters
This research could improve our understanding of how colon cancer develops and spreads,
revealing new ways to treat it. By targeting the interaction between cancer cells and fibroblasts,
I hope to develop therapies tailored to individual patients, leading to better outcomes.