I carry out my research work in the laboratory of Professor Ruth Muschel, the Radiobiology Research Institute, Oxford. I also work in collaboration with the following researchers: Arseniy Yuzhalin, MSc, DPhil student and Keaton Jones, BMBS, BMedSci, MSc, MRCS, DPhil student. My clinical connections include Mr Michael Silva, Mr Srikanth Reddy and Mr Zahir Soonawalla, and all of the Oxford Hepato-Pancreato-Biliary Surgery, Churchill Hospital, Oxford.
I am currently an Academic Clinical Lecturer and Hepatobiliary Surgery SpR within the Oxford Deanery. I completed my undergraduate medical training at the University of Leicester and Warwick in 2006 with honours and undertook an intercalated BSc in 2004 awarded with 1st class honours. I completed my DPhil in the field of Cancer Biology under the supervision of Professor Ruth Muschel (2014).
MBChB, BSc, MRCS, DPhil
Academic Clinical Lecturer and SpR in General Surgery
My research focuses on understanding the biology of liver metastasis.
Liver metastasis is the terminal stage of colon cancer progression. Spread of colon cancer to the liver occurs frequently and understanding the process through this occurs will help to identify new therapies.
My laboratory research explores the relationship between cells found in the metastatic microenvironment and the cancer cells themselves. It is well recognised that the cancer cells make up only a proportion of cells found within a tumour and that some of the non-cancer cells within the tumour actively promote cancer progression.
Our laboratory has identified cells of the immune system that can promote the development of liver metastasis. Using mouse models of liver metastasis we have been able to delay metastatic growth by targeting the immune cells rather than the cancer cells. We have also identified a number of factors release by the tumour-associated immune cells that are responsible for tumour progression.
On-going projects include the use of a novel near infrared imaging device to guide sampling of early liver metastases in patients undergoing liver resection for macroscopic disease. This will enable us to identify factors important for the first phases of metastatic growth in the liver. We are also working on an analysis of structural (extracellular matrix) proteins produced by liver metastases that are important for tumour progression.
Immunohistochemical detection of extracellular matrix proteins (red and green) produced by liver metastases.
Radiation Combined with Macrophage Depletion Promotes Adaptive Immunity and Potentiates Checkpoint Blockade
JONES K. et al, (2018), EMBO Molecular Medicine
Colorectal cancer liver metastatic growth depends on PAD4-driven citrullination of the extracellular matrix.
Yuzhalin AE. et al, (2018), Nat Commun, 9
Dynamic Matrisome: ECM Remodeling Factors Licensing Cancer Progression and Metastasis
yuzhalin A. et al, (2018), Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Radiation-induced immunosuppressive macrophages limit CD8 T-cell mediated tumor killing
MUSCHEL RJ. et al, (2018)
MACROPHAGE DEPLETION OVERCOMES RESISTANCE TO IMMUNE CHECKPOINT BLOCKADE FOLLOWING IRRADIATION
Jones K. et al, (2018), BRITISH JOURNAL OF SURGERY, 105, 45 - 46