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declan.pang@queens.ox.ac.uk

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Declan Pang

BA (Oxon)

DPhil Student

I am taking three years out from the BM BCh Clinical Medicine course at Oxford to undertake a DPhil in Cancer Science. This is under the joint supervision of Professor Fiona Powrie and Professor Deborah Goberdhan.

Colorectal cancer (CRC) is the third most common malignancy worldwide and the fourth leading cause of cancer-related deaths. Current treatment comprises surgical resection and adjuvant chemotherapy but a poor response is observed in 45% of tumours which express a mutation in the KRAS gene, which drives cell proliferation.

The Goberdhan group have identified that CRC cells with KRAS mutations switch to the secretion of a subtype of amphiregulin-containing exosome, when subjected to nutrient stress by glutamine depletion. These exosomes are capable of modulating glutamine metabolism, stimulate angiogenesis and promote tumour growth. In the immune system, the Powrie group have identified detrimental roles for cytokines IL-23 and IL-22, which drive CRC inflammation, and upregulated levels are linked with KRAS mutation. Both are associated with significantly reduced relapse-free survival in stage II/III CRC.

My DPhil aims to unravel the crosstalk between immune signalling and exosome biology in CRC.