Tim Coorens
@timcoorens.bsky.social
560 followers 140 following 31 posts
Research Group Leader at EMBL-EBI | Former postdoc at Broad Institute | Former PhD student at Sanger Institute | Lineage tracing, cancer genomics, human development
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Reposted by Tim Coorens
ebi.embl.org
Welcome @timcoorens.bsky.social ‪ ‬🇳🇱, our new Research Group Leader.

Find out how Tim’s group is exploring using large-scale single-cell and spatial data to trace cell lineages, understand cancer origins, and uncover how mutations drive disease.

www.ebi.ac.uk/about/news/p...
🖥️🧬
Welcome: Tim Coorens
EMBL-EBI’s newest Research Group Leader is investigating how somatic mutations reveal the hidden histories of human cells.
www.ebi.ac.uk
timcoorens.bsky.social
This effort would be impossible without the work of many hundreds of people, including the scientists, the NIH staff, and - of course - the donors and their family. A very exciting time to study somatic evolution and I can't wait to see what the next years bring.
timcoorens.bsky.social
SMaHT will generate massive amounts of data, including short-read, long-read, duplex, single cell DNA, and donor specific assemblies, and much more. Check out our stellar data platform (data.smaht.org), courtesy of our Data Analysis Center in Peter Park's lab - watch this space for future data!
SMaHT Data Portal
data.smaht.org
timcoorens.bsky.social
Underpinning the efforts of the Network is a set of 150 donors from across the US and age range, collected by the NDRI, with many tissues samples for each donor - an absolutely unique collection and momentous effort. Also more info at our consortium website: smaht.org
timcoorens.bsky.social
The SMaHT Network, funded by the NIH Common Fund, has over 300 members from over 50 different institutions all working together on developing new tools and technologies to detect somatic variation, analysing the data in the best way possible, and generating a reference catalog of mosaicism
timcoorens.bsky.social
The cells in our bodies constantly acquire mutations. But what are the patterns of mutations across tissues? How do mutations in normal cells lead to cancer and disease? These are questions we will tackle within the Somatic Mosaicism across Human Tissues (SMaHT) Network, now described in @nature.com
The Somatic Mosaicism across Human Tissues Network - Nature
The Somatic Mosaicism across Human Tissues Network aims to create a reference catalogue of somatic mosaicism across different tissues and cells within individuals.
www.nature.com
Reposted by Tim Coorens
cimususc.bsky.social
Upcoming #CiMUSseminar on Monday ⤵️

🗣 Dr. @timcoorens.bsky.social from @ebi.embl.org :

🧪 "Somatic mutations across normal tissues: past, present, future"

📅 June 30, 1 PM
📍 Theatre room, CiMUS

#RedeCiGUS #FondosEuropeos
‪@mobilegenomes.bsky.social‬ @usc.gal
Reposted by Tim Coorens
gmaci.bsky.social
🚨Chemo treatment upgrade!🚨

Check out our approach to modernise chemotherapy treatment published today in @natgenet.nature.com. From @cniostopcancer.bsky.social #TailorBio @cruk-ci.bsky.social www.nature.com/articles/s41... More details 👇
www.nature.com
Reposted by Tim Coorens
naxerova.bsky.social
Social media grump Kamila has finally made it onto Bluesky!

Please check out my new perspective on metastasis evolution in @natrevcancer.nature.com if you need a reprieve from the news.

I tried my best to develop some new conceptual thoughts here, you be the judge whether I succeeded.
Reposted by Tim Coorens
smahtnetwrk.bsky.social
Keeping you in the loop! ➰
Our Linktree includes all SMaHT websites and social media accounts for easy and consistent access.

Find all our social media accounts in one place:
linktr.ee/smahtnetwork
SMaHT Network | Instagram, Facebook | Linktree
Aiming to transform our understanding of somatic mosaicism.
linktr.ee
Reposted by Tim Coorens
bloodgenes.bsky.social
Thrilled to see my #MITS25 talk brought to life by the brilliant 🎨 @atjcagan.bsky.social! Dive into the stellar science from @g-agarwal.bsky.social & co - fresh on bioRxiv: www.biorxiv.org/content/10.1...
#Genomics #SomaticEvolution
timcoorens.bsky.social
Thanks again for coming over to speak! It was an amazing talk
timcoorens.bsky.social
Thanks very much, Daniel!
timcoorens.bsky.social
Thanks to all the donors and their families for making this study possible. And many thanks to Grace Collord, Peter Campbell, @imartincorena.bsky.social , SY Leung, Mike Stratton and all other co-authors. @broadinstitute.org @sangerinstitute.bsky.social
timcoorens.bsky.social
In short, the normal stomach shows a landscape of somatic mutations with many differences from those of other organs. Our findings provide insights into intrinsic and extrinsic influences on somatic evolution in the gastric epithelium in healthy, precancerous and malignant states
timcoorens.bsky.social
Because we used the LCM approach, we can map these driver clones to their location in tissues, which reveals expansions of mutant clones and local selective pressures. We find three CTNNB1 mutant clones right next to one another, rather than evenly distributed.
timcoorens.bsky.social
Lastly, the stomach also shows a rich landscape of driver mutations, most notably in epigenetic modifiers (ARID1A, ARID1B, KDM6A) and surprisingly inactivating mutations in CTNNB1 (unlike the activating ones observed in cancer).
timcoorens.bsky.social
Glands with trisomies were not associated with a specific stomach region, and their incidence does not linearly increase with age, but are associated with severe chronic inflammation. It's plausible these are a consequence of an exposure, a pathogen or otherwise, long before the time of sampling.
timcoorens.bsky.social
Intriguingly, these trisomies happen multiple times in the same donor, with different alleles amplified. In one case, we found trisomies in 9 of 12 glands sampled. Timing analysis shows these all happened around the same time, suggesting a sudden burst or selective advantage.
timcoorens.bsky.social
The most surprising finding, however, comes from the CNVs in the stomach. We find extraordinarily high rates of somatic whole-chromosome gains/trisomies in the stomach, mostly of chrs 20 and 13, highly concentrated in a few patients.
timcoorens.bsky.social
While SBS17 is very common in gastric cancer, we only find it very rarely in normal glands, and only in very low proportions. So while stomach cells can get exposed to SBS17, high levels of SBS17 seem to be exclusive to overt cancer.
timcoorens.bsky.social
The mutational signatures are mostly SBS1, SBS5 and SBS18, like other epithelial tissues. Metaplastic glands have much more SBS1 and SBS18 (ROS), and indels linked to polymerase slippage. These are also dominant in intestinal glands, so may suggest a “rewiring” of the mutation rate.