Better late than never! The Rendo Lab website is officially up and running 🧠 🧬 Read about our ongoing research and the wonderful team that makes it happen!
rendolab.org

Working hard with @mllthingsdna.bsky.social @katemiro.bsky.social @ms01.bsky.social and @vrendo.bsky.social @embo.org #ChromoPloidy25

Chromosome Segregation and Aneuploidy Aneuploidy is a hallmark of cancer and developmental disorders such as Down syndrome. Understanding how cells accomplish faithful chromosome segregation and how chromosomal instability (CIN) impacts …

Excited to get the #EMBOChromoploidy meeting started! 3 days of fantastic science and fun in beautiful Stresa are beginning now!

meetings.embo.org/event/25-ane...

Thanks so much! 🙏🏻

5/5 Thank you to all the funding agencies that made this research possible, in my case @vetenskapsradet.bsky.social, Cancerfonden, and the Berth von Kantzows Foundation.

4/5 Thank you @rameenberoukhim.bsky.social and @bandolab.bsky.social for your constant trust, mentorship and support, let's hope this is the first of many more papers to come!

3/5 Words cannot describe how thrilled I am to see this paper out! It's not only my first publication as a senior author, but also the result of a wonderful collaboration with the dream team Jeremiah Wala, Simona Dalin, Sophie Webster, and others! 🤩

2/5 We mimic BRD4 focal deletions using CRISPR-Cas9 technology and show that these focal deletions rescue ovarian cancer cells from toxicity associated with BRD4 overexpression, suggesting that BRD4 levels must be fine-tuned for cancer cell proliferation.

1/5 In this case, we describe breakpoints in the BRD4 locus, which rescue gene overexpression toxicity in breast and ovarian cancers with chromosome 19 gains.

Recurrent breakpoints in the BRD4 locus reduce toxicity associated with gene amplification Wala et al. identify recurrent focal BRD4 deletions in tumors harboring larger amplifications, suggesting that these deletions may serve to limit toxic BRD4 overexpression. A CRISPR-Cas9 cell line mod...

📣 Online now! Our study shows how recurrent focal deletions constitute a mechanism by which cancer cells can dampen toxicity due to gene amplification.

www.cell.com/cell-genomic...

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Thanks Mimi, so grateful for your mentorship. Cheers to all the collaborations ahead!

That's so kind of you! Thank you for a brilliant seminar today, and welcome to Uppsala! 😊

Today we celebrated my official Group Leader appointment and paper publications with bubbles and prinsesstårta, the Swedish way! 🍰🥂🍾 Skål!

Thanks so much, John! 🙏🏻❤️

A window-of-opportunity trial reveals mechanisms of response and resistance to navtemadlin in patients with recurrent glioblastoma In patients with glioblastoma, navtemadlin resistance is not mediated by TP53-inactivating mutations, and combination with TMZ may improve efficacy.

So excited to see this paper out! An example of how window of opportunity trials can help dissect the mechanisms of response and resistance associated with targeted therapies in glioblastoma 🧠
www.science.org/doi/10.1126/...
Thanks to the patients and scientific team who made this study possible.

12/ A big acknowledgement to all of our collaborators, as well as the different institutions and foundations who supported our research, including @ec.europa.eu @braintumourcharity.bsky.social @vetenskapsradet.bsky.social @ercresearch.bsky.social

11/ Overall, our study establishes a compendium of genes compensated across human cancers, with functional evidence for toxicity effects associated with gene overexpression in the context of this disease. Many targets to explore pan-cancer and in specific tumor types!

10/ RBM14 amplification (which occurs in the CCND1 locus) is clinically actionable! We find that RBM14 amplification status is correlated with survival in a recently published cohort of >1000 colorectal cancer patients treated with irradiation as standard of care.

9/ We additionally find that RBM14 overexpression can induce an innate immune response, activating the STING-STAT3 axis (we interpret changes in STING perinuclear localization as a marker of pathway activation) and rendering cells more sensitive to STAT3 inhibition.

8/ Given its role in c-NHEJ-mediated DNA repair, we evaluated the effects of RBM14 overexpression in DNA damage response. We found that gene overexpression increases reliance on DNA repair by c-NHEJ (an error-prone process) over HR, increasing the rate of aberrant cell divisions.

7/ We observe a similar effect with RBM14, encoding a member of the family of RNA binding proteins and the HDP-RNP paraspeckle complex. RBM14 is focally amplified on chromosome 11 and results toxic to breast and lung cancer cells when overexpressed.

6/ The well-known cell cycle inhibitor CDKN1A (p21) is an ARGOS gene amplified at the arm-level in chromosome 6p. By creating inducible cell line models, we show that overexpression of CDKN1A impairs the growth of breast cancer cells.

5/ The overlap between “compensated” and “toxic” genes identified eight ARGOS gene candidates across cancers, from which we selected CDKN1A and RBM14 for follow-up validation.

4/ By analyzing data from 17 ORF screens conducted by many of our wonderful collaborators and co-authors
@broadinstitute.org, we identify many genes that result detrimental (i.e. cause growth inhibition or cell death) to cancer cells when overexpressed. We term these “toxic genes”.

3/ The expression of these collaterally altered genes should scale with their copy number. However, by integrating data from >8000 tumors in TCGA & CCLE, we identify amplified genes that are consistently expressed at lower levels than expected, and term them “compensated genes”.

2/ Our study stems from the observation that large chromosomal regions are often gained or lost in cancer. These copy number changes impact not only driver genes but also nearby genes, which become “collaterally altered”.

1/ We describe a new class of cancer genes which we have termed ARGOS. Just like the multi-eyed giant in Greek mythology, ARGOS genes have multiple copies in cancer cells, yet are expressed at lower levels than expected by their copy number and result toxic when overexpressed.

A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer - Nature Communications In cancer, the impact on cellular fitness of copy-number gains affecting collaterally-amplified genes remains poorly understood compared to oncogenes. Here, the authors integrate genomic data from tum...

So excited to see our paper describing the class of ARGOS genes in cancer out in @naturecomms.bsky.social! 🤩
www.nature.com/articles/s41...
A giant effort led with @ms01.bsky.social and executed under the mentorship of @bendavidlab.bsky.social @rameenberoukhim.bsky.social @foijer-lab.bsky.social
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