My research interests include clonal evolution in colorectal adenomas and inflammation-associated cancer, the nature of Barrett’s glands, and the design of methods to explore neutral drift in stem cell divisions in normal human tissues.
Quantification of crypt and stem cell evolution in the normal and neoplastic human colon. Cell Rep (2014) 21;8(4):940-7. PMID: 25127143
The stem cell organisation, and the proliferative and gene expression profile of Barrett's epithelium, replicates pyloric-type gastric glands. Gut (2014) 18. pii: gutjnl-2013-306508. doi: 10.1136/gutjnl-2013-306508. [Epub ahead of print] PMID: 24550372
Lineage tracing reveals multipotent stem cells maintain human adenomas and the pattern of clonal expansion in tumor evolution. Proc Natl Acad Sci U S A (2013) 110(27):E2490-9. PMID: 23766371
I am Emeritus Professor of Histopathology at the Barts Cancer Institute.
My research interests include clonal evolution in colorectal adenomas and inflammation-associated cancer, the nature of Barrett’s glands, and the design of methods to explore neutral drift in stem cell divisions in normal human tissues.
My work included designing methods for the analysis of stem cell biology in human tissues with the aim of understanding the role of stem cells in the maintenance of normal tissue architecture and the progression to malignancy.
We championed the use of mutations in mitochondrial and genomic DNA as clonal markers, and combined these with the analysis of methylation patterns in non-expressed genes to give a time dimension to the clonal expansion of stem cells in normal and malignant tissues.
Thus we have been able to show the location of the stem cell niche in a number of tissues, including the prostate, gastrointestinal and liver epithelia, and to explore clonal expansion of mutant clones in Barrett’s oesophagus, gastric intestinal metaplasia and colorectal adenomas.
We were also been able to follow the development of pre-tumour clones in the colon during pre-neoplastic evolution in Crohn’s disease and ulcerative colitis.
Career