Cancer and Immunogenetics
The fundamental genetics and biology of colorectal cancer (CRC) and their potential applications
We use a panel of over 100 colorectal cancer (CRC) cell lines to study the basic biology of colorectal cancer as well as the effects that new treatments have on the cancer cells. The cell lines have been extensively characterised for genetic mutations, expression profiles and growth characteristics. The use of this number of cell lines allows the identification of subsets of cancers that behave similarly with respect to their biology, drug responses and growth characteristics. This, in turn, allows us to identify the molecularly defined profiles that correlate with, and can ultimately be used to predict for, those responses. Cancer stem cells can be isolated from within individual cell lines and we are also trying to identify the genes that control stemness and cellular differentiation in CRCs.
Recently, we have developed a protocol that allows efficient establishment of medium to long-term primary cultures from fresh CRC tumour material. These are now being compared with the cell lines, both with respect to their biological properties and their drug responses.
Cancer cells grown in 3D can sometimes still form highly organised structures. The central yellow ring of staining identifies the inner luminal surface of this polarised colony of colorectal cancer cells.
The characterisation and population distribution of genetic diversity in human populations, especially of the British Isles
We have collected DNA samples from people in rural areas of the UK whose grandparents all come from within a small geographic radius. This is to reduce the effects of interbreeding between diverse populations, which has the effect of removing ancient regional differences. This serves as a very effective set of healthy controls for genetic studies into the causes of common diseases such as diabetes, psoriasis and schizophrenia. We have analysed Single Nucleotide Polymorphism data from our samples and shown a strong connection between geography and genetic variation. The genetics of normal differences, particularly facial features, are also being investigated; to this end, we are assembling a database of 3D photographs from volunteers whose genotype data we also have. Read more about the project on the PoBI website.
Lead Principal Investigator
Related Research Themes
Related Links
Selected Publications
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The fine-scale genetic structure of the British population.
Journal article
Leslie S. et al, (2015), Nature, 519, 309 - 314
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Rapidly derived colorectal cancer cultures recapitulate parental cancer characteristics and enable personalized therapeutic assays.
Journal article
Ashley N. et al, (2014), J Pathol, 234, 34 - 45
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Stem cell differentiation and lumen formation in colorectal cancer cell lines and primary tumors.
Journal article
Ashley N. et al, (2013), Cancer Res, 73, 5798 - 5809
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People of the British Isles: preliminary analysis of genotypes and surnames in a UK-control population.
Journal article
Winney B. et al, (2012), Eur J Hum Genet, 20, 203 - 210
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Direct and immune mediated antibody targeting of ERBB receptors in a colorectal cancer cell-line panel.
Journal article
Ashraf SQ. et al, (2012), Proc Natl Acad Sci U S A, 109, 21046 - 21051