Dr Guia Cerretelli
Post-Doctoral Visiting Scientist
Intestinal tumour modelling and DNA damage: investigating the role of DNA mismatch repair in ethanol induced colorectal carcinogenesis
Ethanol is a known risk factor for colorectal cancer and is classified (along with its metabolite acetaldehyde) as a group one carcinogen by the International Agency for Research on Cancer. We aim to elucidate the mechanisms of ethanol induced colorectal carcinogenesis, in particular in defective mismatch repair driven tumour formation. Colorectal cancers (CRC) have defective DNA Mismatch Repair (MMR) in ~13% sporadic CRCs mostly due to acquired MLH1 promoter methylation and in ~3% CRCs due to inherited MMR gene mutations in Lynch Syndrome. This project will test the hypothesis that the MMR pathway is involved in repair of some of the ethanol/acetaldehyde-induced DNA base adducts and thus ethanol is likely to accelerate dMMR-driven intestinal tumour formation via unrepaired DNA damage.
Cerretelli G, Zhou Y, Müller MF, Adams DJ, Arends MJ, "Ethanol-induced formation of colorectal tumours and precursors in a mouse model of Lynch syndrome", J Pathol. 2021 Dec;255(4):464-474. doi:10.1002/path.5796, Epub 2021 Oct 13, PMID: 34543445
Cerretelli G, Ager A, Arends MJ, Frayling IM, "Molecular pathology of Lynch syndrome." J Pathol. 2020 Apr;250(5):518-531, doi:10.1002/path.5422, PMID: 32141610
Rashid M, van der Horst M, Mentzel T, Butera F, Ferreira I, Pance A, Rütten A, Luzar B, Marusic Z, de Saint Aubain N, Ko JS, Billings SD, Chen S, Abi Daoud M, Hewinson J, Louzada S, Harms PW, Cerretelli G, Robles-Espinoza CD, Patel RM, van der Weyden L, Bakal C, Hornick JL, Arends MJ, Brenn T, Adams DJ, "ALPK1 hotspot mutation as a driver of human spiradenoma and spiradenocarcinoma", Nat Commun. 2019 May 17;10(1):2213, doi:10.1038/s41467-019-09979-0, PMID: 31101826