Mike Spencer Chapman Profile
Mike Spencer Chapman

@doctor_msc

Followers
547
Following
375
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28
Statuses
330

Haematology doctor & researcher, UK. Interested in blood ageing, transplant, cancer and development. Lapsed musician.

N 51°27' 0'' / W 0°6' 0''
Joined October 2011
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@doctor_msc
Mike Spencer Chapman
6 months
So pleased to have the paper out, available here: For me this was discovery science as I had always hoped it would be. Unpredictable, a lot of fun, and some proper detective work with plenty of twists & turns on the way. Brief thread below 🧵.
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@doctor_msc
Mike Spencer Chapman
5 months
Thank you HaemStar! It was a great day, lots of exciting & motivating talks - really recommend future events to all haem trainees/ those interested in choosing haem training.
@HaemSTAR_UK
HaemSTAR 💙
5 months
Fair to say we were all blown away by the incredible work of @doctor_msc. Taking us back to science basics with his work on phylogenies and clonal dynamics. A truly dynamic and captivating talk! Thank you so much for joining us at #haemSTAR25
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@doctor_msc
Mike Spencer Chapman
6 months
RT @S_J_Aitken: @doctor_msc @mst_paralogue Congratulations on your elegant paper! It's great to see #LesionSegregation being identified in….
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@doctor_msc
Mike Spencer Chapman
6 months
RT @TimePieChina: In a paradigm shift in how we view mutations, researchers uncover forms of DNA damage in healthy cells that can persist u….
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@doctor_msc
Mike Spencer Chapman
6 months
RT @sangerinstitute: DNA damage can go unrepaired for years, which can create multiple chances to generate harmful mutations that could lea….
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@doctor_msc
Mike Spencer Chapman
6 months
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 & @TimCoorens for valuable input.
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@doctor_msc
Mike Spencer Chapman
6 months
Also, the whole idea of these persistent lesions builds on the concept of 'lesion segregation' observed (again, unexpectedly) and developed by @S_J_Aitken @mst_paralogue and team.
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@doctor_msc
Mike Spencer Chapman
6 months
This discovery science is only possible thanks to the large-scale somatic phylogeny datasets re-analysed here, generated by @Emily_LMitchell @StanleyWKNg @WilkMatthias @TheBoettcherLab @ken1_yossy @jyoti_nangalia & others, funded by @CR_UK @sangerinstitute @wellcometrust +others.
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@doctor_msc
Mike Spencer Chapman
6 months
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.
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@doctor_msc
Mike Spencer Chapman
6 months
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.
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@doctor_msc
Mike Spencer Chapman
6 months
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’)
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@doctor_msc
Mike Spencer Chapman
6 months
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’).
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@doctor_msc
Mike Spencer Chapman
6 months
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.
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@doctor_msc
Mike Spencer Chapman
6 months
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).
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@doctor_msc
Mike Spencer Chapman
6 months
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.
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@doctor_msc
Mike Spencer Chapman
6 months
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'
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@doctor_msc
Mike Spencer Chapman
6 months
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 today came from just such a blip. So don’t ignore the weird stuff. Pull on that thread.
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@doctor_msc
Mike Spencer Chapman
6 months
RT @QMBCI: 📰 Some forms of DNA damage linger unrepaired in healthy cells for years, according to a @Nature study led by Dr Mike Spencer Cha….
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@doctor_msc
Mike Spencer Chapman
6 months
RT @S_J_Aitken: Building on our discovery of #LesionSegregation, @doctor_msc and colleagues from @sangerinstitute find that some DNA lesion….
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@doctor_msc
Mike Spencer Chapman
8 months
Fascinating stuff! Lots to learn about these structures. Congratulations Chris! 🎉.
@cbailey_58
Chris Bailey
8 months
Hot off the press!! 🔥 Check out our work on the origins and impact of ecDNA. This was a team effort involving multiple collaborators as one of a three part series on ecDNA in @Nature.
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