Nat Peckett
Project: "Plasticity in the gastrointestinal tract in health and disease: The role of ATRX in colorectal cancer metastasis."
Medical Student Essay Prize Winner 2025
Dr Peckett explains:
“ATRX is a chromatin-remodelling helicase, implicated in regulating both Epithelial-mesenchymal transition (EMT) and metastasis in Colorectal Cancer (CRC) and is one of the most commonly mutated genes in the cancer process. The aim of my project was to focus on determining the mechanism by which ATRX loss regulates cell plasticity and metastasis.
Using research techniques, I investigated the effects of ATRX loss on the chromatin landscape and how this was associated with ATRX loss phenotype and behaviour, along with the co-regulatory roles of other transcription factors in this process. We found that ATRX mutation occurs in 7% of CRCs and is associated with late-stage metastatic disease and poor survival in patients, particularly in the highly aggressive CRIS-B subtype. We also discovered that the deletion of ATRX in a mouse CRC organoid model resulted in an aggressive phenotype, including increased propensity to induction of epithelial-to-mesenchymal transition (EMT), tumour invasion and metastasis. We further observed a loss of transcriptional colonic epithelial identity and emergence of highly plastic mesenchymal and squamous-like cell states.
We believe that ATRX loss results in loss of chromatin accessibility at key colonic epithelial gene loci, thus preventing epithelial transcription factors from binding, and resulting in the softening of colonic epithelial identity, which is central to the ATRX loss phenotype. It is this loss of identity that allows for increased cellular plasticity and supports the gain of unorthodox gene expression.
I further explored the role of an EMT programme in our metastatic CRC models. We wanted to determine whether the EMT process is fundamental to metastasis, or whether it is just one example of phenotypic plasticity. My findings challenge the classical view of EMT and suggest that it is cellular plasticity, rather than the adoption of any particular cell state(s), that is critical for metastatic progression.”
What did it feel like to win this award?
This award has encouraged me to think about how my research fits more broadly into the gastroenterology field, outside of being specific to cancer and oncology. It has also provided me with the opportunity to attend the annual BSG conference to learn more about gastroenterology as a speciality and what career opportunities it holds.
Read more about Dr Peckett’s project, focused on the gut, by downloading the PDF below.
