Contact information
Professor KJ Patel
FRS FMedSci
MRC WIMM Director, MRC MHU Director
We study endogenous DNA damage and its impact on the function of vertebrate stem cells and the ageing process. Our recent work has shown that metabolism releases reactive aldehydes that are a potent source of such endogenous DNA damage. Mammals are protected against these genotoxic metabolites by first eliminating them through oxidising enzymes, and secondly by repairing the DNA damage they cause.
Our current research aims to define the origins and identity of genotoxic metabolites, how cells remove them, the nature of the DNA damage they cause and how this damage is repaired. We are also want to understand how certain stem cells and organ systems are damaged by these sources of endogenous DNA damage, and the consequences of this to an organism.
Key publications
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Aldehyde-driven transcriptional stress triggers an anorexic DNA damage response.
Mulderrig L. et al, (2021), Nature, 600, 158 - 163
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Alcohol-derived DNA crosslinks are repaired by two distinct mechanisms.
Hodskinson MR. et al, (2020), Nature, 579, 603 - 608
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Alcohol and endogenous aldehydes damage chromosomes and mutate stem cells.
Garaycoechea JI. et al, (2018), Nature, 553, 171 - 177
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Mammals divert endogenous genotoxic formaldehyde into one-carbon metabolism.
Burgos-Barragan G. et al, (2017), Nature, 548, 549 - 554
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Endogenous Formaldehyde Is a Hematopoietic Stem Cell Genotoxin and Metabolic Carcinogen.
Pontel LB. et al, (2015), Mol Cell, 60, 177 - 188
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Genotoxic consequences of endogenous aldehydes on mouse haematopoietic stem cell function.
Garaycoechea JI. et al, (2012), Nature, 489, 571 - 575
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Two Aldehyde Clearance Systems Are Essential to Prevent Lethal Formaldehyde Accumulation in Mice and Humans.
Dingler FA. et al, (2020), Mol Cell, 80, 996 - 1012.e9
Recent publications
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Embracing cancer complexity: Hallmarks of systemic disease.
Swanton C. et al, (2024), Cell, 187, 1589 - 1616
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Aldehyde-mediated inhibition of asparagine biosynthesis has implications for diabetes and alcoholism.
John T. et al, (2024), Chem Sci, 15, 2509 - 2517
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Formaldehyde regulates S-adenosylmethionine biosynthesis and one-carbon metabolism.
Pham VN. et al, (2023), Science, 382
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Genotoxic aldehyde stress prematurely ages hematopoietic stem cells in a p53-driven manner.
Wang M. et al, (2023), Mol Cell
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A histone deacetylase 3 and mitochondrial complex I axis regulates toxic formaldehyde production.
Wit N. et al, (2023), Sci Adv, 9