Holly Eggington

Morphogen regulation of cellular differentiation and plasticity across model systems of colorectal cancer

Colorectal cancer poses a significant burden of disease globally. However, these cancers do not appear fully-formed. Instead, pre-cancerous lesions develop into cancers, although many are not spotted until they have become full cancers, as this is the point at which symptoms begin to develop. However, with improved screening programs, we are improving our ability to find these lesions earlier and earlier. Despite this, intervention remains the same, largely being in the form of either observation, or surgical intervention.

My research aims to assess key molecular disruption in order to investigate the transition from pre-cancer to cancer, with the aim of finding novel approaches to apply in the pre-cancer setting. This has been achieved by:

1)      Utilising originally generated and publicly available gene expression datasets in order to identify key alterations in gene regulation in the adenoma to carcinoma transition. This is married with assessment of the ‘on-slide’ phenotype of immune and stromal populations.

2)      From this, identification of putative points of potential intervention in established adenomas, both in murine model systems and organoid models to assess degree of potential amelioration of disease phenotype belied by molecular intervention, with a focus on the BMP (bone-morphogenic protein) and YAP (yes-associated protein) pathways.

3)      Further translation of prior identified morphogen manipulation efficacy to a preventative setting, where introduction prior to point of pre-cancer establishment is assessed for potential to prevent neoplasia establishment and outgrowth, in organoid and murine model systems.

How could your research ultimately benefit patients

Preventing disease progression is a key point of research in the field of cancer prevention. Established polyps may only be treated currently by surgical resection, which has a notable quality of life impact, and may be an unsuitable option for many patients. However, polyps left untreated show high risk of progression to cancer. Through identification of potential non-surgical approaches to treating established pre-cancer, as well as treatments which may prevent phenotype onset in families with cancer predisposing syndromes such as familial adenomatous polyposis (FAP).  

About Holly

I started studying at Oxford Medical School in 2016, although had always been keen to specialise in oncology and contribute to cancer research as I progressed my medical career, as this was a key motivator in my application to medical school. The establishment of the DPhil in Cancer Science programme, and the specialised track for medical students in particular, encouraged me to consider undertaking a DPhil as an intercalated component of my studies. I really enjoyed the work I carried out in a pre-clinical setting as part of my Final Honours School project in the final year of my BA degree, and was excited to get to expand my experience to cancer-specific pre-clinical research as part of my DPhil in the Leedham group, where we specialise in preclinical research into gastrointestinal cancers and inflammation settings, with a particular focus on stem cells and interaction of different tissue compartments in this setting. In the future, I hope to integrate my experience of preclinical research to a patient-based setting as I return to clinical practice. 

What does your DPhil experience look like day-to-day?

Due to constrains of COVID during the first year of my DPhil, I had the opportunity to undertake bioinformatic training, both through independent study and the support of my lab's bioinformatician, which allowed me to integrate bioinformatic study as well as wet-lab work into my studies. I tend to split my time between bioinformatic work, histology workflows, including immunohistochemistry and in-situ hybridisation approaches, and organoid studies. My day to day is very variable depending on the current experiments taking place, but weekly usually includes cell culture experiments, maintenance of mouse colonies or mouse experiments, and data analysis of previously collected data. This, in parallel with implementation of numerous bioinformatics approaches, leads to a very busy workflow with lots of variability in techniques and applied knowledge! 

If you had to name one thing, what is your greatest achievement since starting your DPhil?

I was lucky enough in the third year of my DPhil to receive a short-term JSPS fellowship, where I had the opportunity to visit Keio University in Tokyo and study intestinal organoid biology and CRISPR-Cas9 gene editing with Professor Toshiro Sato for three months. This was a fantastic opportunity to learn some really cutting-edge science with a leading expert in the field, as well as providing an incredible opportunity to travel Tokyo and wider Japan in my free time. This was a phenomenal opportunity which I wouldn’t have been able to explore without the experiences and freedom offered through the undertaking of my DPhil.

Accolades and Key Publications 

JSPS Short-term Research Fellow 2023 - Keio University, Tokyo (March-June 2023)

President of Oxford Personalised Medicine Society (2021-2022)

Student Representative, Centre for Personalised Medicine, Oxford (2020-2021)

College Tutor in Medical Genetics and Cancer Science (2019-Present)

Recipient of St Anne’s Graduate Development Scholarship (2023-2024, 2024-2025)

Eggington HR, Mulholland EJ, Leedham SJ. Morphogen regulation of stem cell plasticity in intestinal regeneration and carcinogenesis. Dev Dyn. 2022 https://doi.org/10.1002/dvdy.434

Vasquez EG, Nasreddin N, Valbuena GN, Mulholland EJ, Belnoue-Davis HL, Eggington HR, Schenck RO, Wouters VM, Wirapati P, Gilroy K, Lannagan TRM, Flanagan DJ, Najumudeen AK, Omwenga S, McCorry AMB, Easton A, Koelzer VH, East JE, Morton D, Trusolino L, Maughan T, Campbell AD, Loughrey MB, Dunne PD, Tsantoulis P, Huels DJ, Tejpar S, Sansom OJ, Leedham SJ. Dynamic and adaptive cancer stem cell population admixture in colorectal neoplasia. Cell Stem Cell. 2022 https://doi.org/10.1016/j.stem.2022.07.008