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mattcoelho.bsky.social
Matt Coelho
@mattcoelho.bsky.social
140 followers 110 following 22 posts
Cancer Research UK Career Development Fellow at the Wellcome Sanger Institute - gene editing - drug resistance - cancer
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mattcoelho.bsky.social
Matt Coelho @mattcoelho.bsky.social · 20h
A pleasure to talk about our research today with the amazing volunteers at St John’s ambulance in aid of @cancerresearchuk.org
Reposted by Matt Coelho
eventswcs.bsky.social
Wellcome Connecting Science Learning and Training @eventswcs.bsky.social · Jul 17
Apply for Multiplex Assays of Variant Effects training by 18 August! ⏰

Join our experts to learn how to strengthen your genetic disease research or clinical work using MAVE data. 🧬

Financial assistance available💸

📎Find out more: bit.ly/3EW3lh4
#MAVE25 #VariantInterpretation
Wellcome Connecting Science Multiplex Assays of Variant Effects Course dates: 23-28 November 2025 Location: Wellcome Genome Campus, UK Application and bursary deadline: 18 August - apply now
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Reposted by Matt Coelho
varianteffect.bsky.social
Atlas of Variant Effects Alliance @varianteffect.bsky.social · Aug 7
Coming up in September!
➡️Christina Kajba @ckajba.bsky.social & Michael Herger @michaelherger.bsky.social — pooled prime editing screens in haploid human cells
➡️Jon Acosta — multiplexed in vivo base editing screens
#GeneticVariants #PrimeEditing
ℹ️https://www.varianteffect.org/seminar-series/
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Reposted by Matt Coelho
natbiotech.nature.com
Nature Biotechnology @natbiotech.nature.com · Aug 7
Natural molecular glues spur next-gen small molecules for ‘undruggable’ targets www.nature.com/articles/s41...
Natural molecular glues spur next-gen small molecules for ‘undruggable’ targets - Nature Biotechnology
Inspired by natural molecular glues, drug hunters are chasing protein–protein interactions with next-gen small molecules tuned for enhanced tissue specificity and reduced toxicity.
www.nature.com
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mattcoelho.bsky.social
Matt Coelho @mattcoelho.bsky.social · Jul 25
mattcoelho.bsky.social
Matt Coelho @mattcoelho.bsky.social · Jul 25
Looking to combine ML and functional genomics to tackle cancer drug resistance? Exciting job opening at the Sanger!

sanger.wd103.myworkdayjobs.com/en-US/Wellco...
Principal Software Developer/Computational Biologist
Do you want to help us improve human health and understand life on Earth? Make your mark by shaping the future to enable or deliver life-changing science to solve some of humanity’s greatest challenge...
sanger.wd103.myworkdayjobs.com
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Reposted by Matt Coelho
isabellease.bsky.social
Isabelle Zane @isabellease.bsky.social · May 22
@mattcoelho.bsky.social at #VariantEffect25
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Reposted by Matt Coelho
cansudincer.bsky.social
Cansu Dinçer @cansudincer.bsky.social · May 22
🚨 Excited to share our latest preprint!
@mgarnett.bsky.social @mattcoelho.bsky.social
We introduce BEstimate, a flexible, comprehensive tool for designing and interpreting CRISPR-based editing experiments.
#CRISPR #BEstimate #BaseEditor
biorxivpreprint.bsky.social
bioRxivpreprint @biorxivpreprint.bsky.social · May 20
BEstimate: a computational tool for the design and interpretation of CRISPR base editing experiments https://www.biorxiv.org/content/10.1101/2025.05.19.654892v1
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Reposted by Matt Coelho
isabellease.bsky.social
Isabelle Zane @isabellease.bsky.social · May 21
Magdalena Strauss at #VariantEffect25
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Reposted by Matt Coelho
benlehner.bsky.social
Ben Lehner @benlehner.bsky.social · May 6
Come and join us! We’re hiring a new Group Leader in Generative Biology at the @sangerinstitute.bsky.social

Building AI models or the data to train them?

Core funding of >$130M a year for a faculty of ~30.

www.nature.com/naturecareer...

acrobat.adobe.com/id/urn:aaid:...

pls RT!
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mattcoelho.bsky.social
Matt Coelho @mattcoelho.bsky.social · Apr 22
This was a fantastic international collaboration with the @mgarnett.bsky.social, Halim and Voest teams. Thank you and congrats to all the co-authors, especially Alex, @gabrielepicco.bsky.social, Vivien and Youhani.
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mattcoelho.bsky.social
Matt Coelho @mattcoelho.bsky.social · Apr 22
Finally, in patients, tumors with lower CHD1 and MAP3K7 expression responded better to cancer immunotherapy, suggesting that these genes could serve as biomarkers of response to ICB.
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mattcoelho.bsky.social
Matt Coelho @mattcoelho.bsky.social · Apr 22
In mice, knocking out these genes in tumour cells led to improved responses to immune-checkpoint blockade (ICB) and increased T cell numbers and activation in tumours.
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mattcoelho.bsky.social
Matt Coelho @mattcoelho.bsky.social · Apr 22
CHD1 and MAP3K7 KO additively sensitises cancer cells to IFN-g, TNF-a and T cells and are known activators of NF-kB signalling. RNA-seq revealed they regulate the transcriptional response to cytokines involving the TF CDX2, overall switching the cell response from apoptosis to cell survival.
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mattcoelho.bsky.social
Matt Coelho @mattcoelho.bsky.social · Apr 22
We also identified known regulators of cytokine signalling as hits in our cytokine and T cells screens across multiple cell contexts (e.g. TBK1, SOCS1, ADAR), allowing us to compare the against CHD1 and MAP3K7 KO and unpick the signalling pathways involved in each case.
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mattcoelho.bsky.social
Matt Coelho @mattcoelho.bsky.social · Apr 22
Interestingly, CHD1 and MAP3K7 are co-lost in several common cancer types, such as prostate, thyroid and melanoma (~4 %), with higher rates of loss of either gene alone.
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mattcoelho.bsky.social
Matt Coelho @mattcoelho.bsky.social · Apr 22
Through integrating these data, we identify CHD1 and MAP3K7 as key determinants of resistance to T cell attack. Our individual cytokine screens and the use of JAK1/2 KO isogenic cancer cell models allowed us to deconvolute different contributions of cytokines on T cell-mediated killing.
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mattcoelho.bsky.social
Matt Coelho @mattcoelho.bsky.social · Apr 22
These T cells are derived from the same patient as the tumoroids - endogenous neoantigen expression drives reactivity. Special thanks to our collaborators from the Voest lab for pioneering this sophisticated system for studying anti-tumour immunity.
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mattcoelho.bsky.social
Matt Coelho @mattcoelho.bsky.social · Apr 22
We used whole-genome CRISPR/Cas9 screens in autologous primary tumoroid T cell co-cultures to investigate genes that modulate cancer cell killing by T cells.
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mattcoelho.bsky.social
Matt Coelho @mattcoelho.bsky.social · Apr 22
We generated a large-scale dataset of context-specific dependencies in 4 cancer cell models, across 4 cytokines and autologous tumour-reactive T cells, collectively encompassing data from >150 whole-genome CRISPR-Cas9 screen samples.
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mattcoelho.bsky.social
Matt Coelho @mattcoelho.bsky.social · Apr 22
Excited to announce our preprint today @biorxivpreprint.bsky.social
Using functional genomics, we map the genetic determinants cancer cell sensitivity to tumour-reactive T cells:
www.biorxiv.org/content/10.1...
CRISPR screens in the context of immune selection identify CHD1 and MAP3K7 as mediators of cancer immunotherapy resistance
Cancer immunotherapy is only effective in a subset of patients, highlighting the need for effective biomarkers and combination therapies. Here we systematically identify genetic determinants of cancer...
www.biorxiv.org
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mattcoelho.bsky.social
Matt Coelho @mattcoelho.bsky.social · Mar 27
less than one week remaining to apply 👇
mattcoelho.bsky.social
Matt Coelho @mattcoelho.bsky.social · Mar 12
Excited to announce that we're recruiting a Staff scientist at the Sanger Institute to investigate drug resistance mechanisms in cancer using gene editing.

Interested?
Apply here:
sanger.wd103.myworkdayjobs.com/en-US/Wellco...
Reposted by Matt Coelho
mgarnett.bsky.social
Mathew Garnett @mgarnett.bsky.social · Feb 25
New Gordon Research Conference Alert: Synthetic Lethality Approaches in Oncology. www.grc.org/synthetic-le....

Join us 20-25th July 2025 for an intimate meeting with thought leaders in the field. Great for networking and opportunities for early career scientists to present their research.
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mattcoelho.bsky.social
Matt Coelho @mattcoelho.bsky.social · Mar 12
Deadline is 2nd of April
mattcoelho.bsky.social
Matt Coelho @mattcoelho.bsky.social · Mar 12
Excited to announce that we're recruiting a Staff scientist at the Sanger Institute to investigate drug resistance mechanisms in cancer using gene editing.

Interested?
Apply here:
sanger.wd103.myworkdayjobs.com/en-US/Wellco...
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