Matt Coelho

A pleasure to talk about our research today with the amazing volunteers at St John’s ambulance in aid of @cancerresearchuk.org

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

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

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/

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.

Natural molecular glues spur next-gen small molecules for ‘undruggable’ targets www.nature.com/articles/s41...

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...

@mattcoelho.bsky.social at #VariantEffect25

🚨 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

Magdalena Strauss at #VariantEffect25

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!

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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...

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...

less than one week remaining to apply 👇

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.

Deadline is 2nd of April

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...

Thrilled to share new work led by @jieyang437.bsky.social in the lab published today in @Nature. We find that Aspirin prevents metastasis by releasing T cells from immune suppression by platelet TXA2. @Cambridge_Uni @CRUKCamCentre rdcu.be/eci1U

Thank you to the thought leaders from computational biology, physics, oncology and drug discovery who contributed to this workshop, and Cancer Research UK, Rosetrees trust and the Physics of Life Network for organising.

We propose functional genomics and AI approaches to predict resistance early in the drug discovery process. Lastly, learning from the challenges of antimicrobial resistance and the COVID19 pandemic, we propose routes for efficient data sharing to accelerate the translation of research to the clinic.

We outline the Hallmarks of cancer drug resistance, and how disease monitoring and more adaptive, combinatorial treatments guided by genomics could extend patient benefit or mitigate acquired drug resistance.

Breaking barriers: we need a multidisciplinary approach to tackle cancer drug resistance - BJC Reports BJC Reports - Breaking barriers: we need a multidisciplinary approach to tackle cancer drug resistance

Today in BJC Reports, we summarise the outcomes from a multidisciplinary workshop focused on addressing cancer drug resistance.
www.nature.com/articles/s44...