Heather Clark

The complement protein C5a receptor 1 (C5aR1) is expressed on tumour cells and regulates cell fate through interactions with the anaphylatoxin C5a. As such, administering a C5aR1 inhibitor alongside radiotherapy increases NF-κB-dependent apoptosis of tumour cells, whilst protecting intestinal cells from radiotherapy-mediated damage. Little research has been performed into C5aR1-regulated radioprotection, but further elucidation could identify methods to reduce dose-limiting tissue toxicity.

My DPhil project will focus on the role of C5aR1 in regulating the response to radiotherapy in the normal intestinal tissue microenvironment.  I will particularly focus on C5aR1-modulated changes in immune and non-immune populations in irradiated versus non-irradiated intestinal tissues. Techniques used in the first year of my project will likely include multiplex imaging and spatial transcriptomics of murine intestinal tissues, as well as in vitro murine intestinal organoid co-culture assays.

How could your research ultimately benefit patients?

Radiotherapy is frequently used to treat abdominopelvic cancers, particularly localised rectal tumours. However, radiotherapy can damage intestinal tissues adjacent to the irradiated tumour to cause radiation-induced intestinal damage (RIID). Acute cases of RIID correlate with higher rates of treatment interruption, whilst chronic RIID can require surgery and causes death in approximately 1 in 10 of patients with chronic RIID. As radiotherapy is one of the most effective treatments against localised tumours, it is important to find strategies to reduce dose-limiting tissue toxicity. This would ensure appropriate radiotherapy doses can be administered to effectively kill tumour cells, improving patient survival rates and quality of life.

About Heather

I am a first-class ‘Biomedical Sciences’ BSc graduate from the University of Bristol, specialising in cancer and immunology. My research project (supervised by Professor Ann Williams) focussed on the role of the inhibitor of κB (IκB) kinase, B cell lymphoma 3, in colorectal cancer metastasis.

Interested in the role of immune signalling pathways (like NF-κB) in cancer, I worked as a research assistant for 6 months in a computational biology laboratory led by Dr Simon Mitchell (University of Sussex). Here, my work focussed on immunophenotyping NF-κB protein expression in Diffuse Large B-cell Lymphoma (DLBCL) to inform computational models designed to help us better understand NF-κB heterogeneity in DLBCL and stratify targeted therapy selection.

I then studied a MSc by Research in ‘Oncology’ in the laboratory of Dr Monica Olcina (University of Oxford). My project investigated the role of C5aR1 in normal intestinal tissue radioprotection. I was eager to continue my work in the Olcina laboratory to further improve my technical skillset and knowledge of complement function in cancer and radiotherapy response. I hope my DPhil work will contribute to the development of strategies that limit irradiation-associated side effects and improve tumour cell response to therapy.