Oliver Beaven

I completed my undergraduate study at Durham University, graduating 2020, before joining the Patel group as a research assistant in the autumn of that year. In September 2021, I began on the DPhil in Medical Sciences course.

Currently, my focuses is on furthering our understanding of the tier 1 aldehyde protection enzymes, aldehyde dehydrogenase 2 and 5 (ALDH2 and ADH5). Absence of ADH5 leads to the accumulation genotoxic formaldehyde, which can be produced both endogenously, through processes including one-carbon metabolism and histone demethylation, and exogenously from environmental and dietary sources. ALDH2 is more well known in detoxifying the ethanol product, acetaldehyde, and acts specifically within the mitochondria. The Patel lab has shown the significance of these aldehydes in the absence of tier 1 detoxification and tier 2 DNA damage repair enzymes, in contribution to Fanconi anaemia, bone marrow failure, progeria and developmental abnormality. Interestingly, recent work has demonstrated simultaneous loss of both tier 1 enzymes to resemble and extend this two-tier pathology in mice and humans (Dingler et al., 2020). Despite the significance of these proteins, very little is known regarding their cellular activity, particularly ADH5. How are they regulated across different differential or metabolic states? To what degree do they act redundantly in aldehyde detoxification? Do aldehydes interact with transcriptional networks beyond the classical DNA damage response? My research aims to use cell and mouse models to go deeper into these questions and expand our understanding of the signalling landscape that responds to formaldehyde.