Mike Spencer Chapman

Image shows chromosome pairs with abnormal, stunted, chromosome 22 which causes chronic myeloid leukaemia. Credit: Nangalia Research Group.

The abnormal gene which causes chronic myeloid leukaemia has a very strong ability to drive rapid growth of the cancer, research has revealed 🧬

Scientists were able to track the evolution of this gene to study the rate at which the cancer cells expand: bit.ly/42riKOk

Lovely piece from @s-j-aitken.bsky.social and Claudia Arnedo Pec discussing our recent paper in @nature.com on persistent mutagenic DNA lesions... Love the title!

Puts it in the context of their beautiful previous work on lesion segregation

Mitochondrial single cell-multi-omics for lineage tracing and genetics

Interested in 'Mitochondrial single cell-multi-omics for lineage tracing and genetics'? Apply for our free workshop in Berlin following our #ISCO2025 conference!

www.isco-conference.eu

www.mdc-berlin.de/news/events/...

Is hypothesis generation a hindrance to Night Science? @itaiyanai.bsky.social and @stearnslab.bsky.social demonstrated how easy we fall into pattern recognition, missing the “Gorilla” in our own data. Today’s seminar was all about identifying new strategies to stay curious about our own data.

Genetic background sets the trajectory of cancer evolution Human cancers are heterogeneous. Their genomes evolve from genetically diverse germlines in complex and dynamic environments, including exposure to potential carcinogens. This heterogeneity of humans,...

🌟NEW PREPRINT ALERT!🌟

We are very pleased to introduce #StrainDifferences: “Genetic background sets the trajectory of cancer evolution”

www.biorxiv.org/content/10.1...

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Thanks Trevor! I remember this was the PhD chapter that probably sparked the most viva discussion.. ☺️

Thank you!

Ha.. yeah, the big question! Not really unfortunately. We think it is probably structurally non-bulky so as not to substantially stall the replication machinery. And may relate to the hypoxic niche of HSCs. I know others have also speculated that aldehydes may be involved.. Any theories welcome!

Thanks for sharing! And apologies for the cheap kitten meme..

Thank you Maria!

Thanks Andrew. Yeah, an exciting discovery is rarely the end result! But great when it is

Ha! Love it.. need to get a copy of that for my wall

Discovery of lingering DNA damage could change our understanding of cancer development - Barts Cancer Institute - Queen Mary University of London Dr Michael Spencer Chapman and team have uncovered forms of DNA damage in healthy cells that can persist unrepaired for years.

📰 Some forms of DNA damage linger unrepaired in healthy cells for years, according to a @nature.com study led by Dr Mike Spencer Chapman @mikespencerchapman.bsky.social at BCI and @sangerinstitute.bsky.social. 

The findings could inform our understanding of #cancer development. 🧪 #medsky

This is a cool paper about the surprisingly long-term persistence of DNA lesions (single stranded DNA errors) in the human body. Exquisitely meticulous work from conception through to execution. Congratulations @mikespencerchapman.bsky.social

Yes! @s-j-aitken.bsky.social your fantastic work on lesion segregation really was the foundation for this.. gave us early confidence that some lesions were able to persist through multiple cell divisions & that our theory was viable

a close up of a statue of yoda with the words `` thank you wise one '' written below him . ALT: a close up of a statue of yoda with the words `` thank you wise one '' written below him .

A huge thank you to Peter Campbell, my supervisor whose insights were vital to getting this study started. When I showed him the 1st unexpected mutation he said (typically) ‘I wondered if this might happen..’ Also, thanks to @imartincorena.bsky.social & @timcoorens.bsky.social for valuable advice.

Also, the whole idea of these persistent lesions builds on the concept of 'lesion segregation' observed (again, unexpectedly) and developed by
@s-j-aitken.bsky.social , Martin Taylor, Duncan Odom & team.

This discovery science is only possible thanks to the large-scale somatic phylogeny datasets re-analysed here, generated by Emily Mitchell, Stan Ng, Matthias Wilk,Kenichi Yoshida,Jyoti Nangalia+others, funded by @cancerresearchuk.org @sangerinstitute.bsky.social @wellcometrust.bsky.social + others

Intriguingly, blood stem cells had a particular type of very long-lasting damage (~2-3 years), leading to 15-20% of their mutations – some contributing to cancer. This damage wasn’t evident in other tissues. We have theories, but we don’t yet know why.

It was these patterns of unusual mutation inheritance, or multiple different mutations at the same site in closely related cells that was the key to recognizing & characterizing these unusual types of long-lasting damage.

If the base is partially recognizable, the DNA copying machinery may flip between copying it right, and copying it wrong in one specific way. This will only cause 1 mutation, but the pattern of inheritance will not fit a single acquisition event (a ‘phylogeny-violating variant’)

But what if it’s not? If the DNA damage sticks around through multiple rounds of cell division & DNA replication it may be misread in different ways in each round. This will lead to different mistakes at the same position (a ‘multi-allelic variant’).

If the damaged base is present during DNA replication it may be misread, resulting in permanent mutations that can contribute to cancer development. However, the DNA damage itself is usually recognized and mended quickly by repair mechanisms in our cells.

How did we work this out?

DNA damage is distinct from a mutation. While a mutation is one of the 4 standard DNA bases (A, G, T or C) in the wrong place (like a spelling mistake), DNA damage is chemically altered DNA (more like some illegible writing).

After ‘pulling the thread’ we found the explanation. Some specific types of DNA damage persist unrepaired through multiple cell divisions, in some cases for years. This goes against the usual idea that damage is efficiently repaired by the cell’s DNA repair machinery.

I work with somatic phylogenies: family trees of 100s of cells from 1 individual, illustrating their relationships going back to conception. It is inferred from the pattern of shared mutations in the DNA. In 2019 I noticed a mutation that didn’t fit the phylogeny – the 'blip'

So pleased to have the paper out, available here: www.nature.com/articles/s41586-024-08423-8
For me this was discovery science as I had always hoped it would be. A lot of fun, and some proper detective work with plenty of twists & turns on the way. Brief thread below

In science, we often see weird blips in the data. The question: is it artefact (usually!), or something new & exciting? We don’t always have time to dig deep.

Our paper in @nature.com today came from just such a blip. So don’t ignore the weird stuff. Pull on that thread...

I've made the switch! Looking forward to a more inspiring newsfeed.. 🤞