Veronica Rendo
@vrendo.bsky.social
Group Leader, Uppsala University 🇸🇪 |
Studying brain tumor evolution and treatment resistance
Studying brain tumor evolution and treatment resistance
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.
March 19, 2025 at 3:43 PM
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!
March 19, 2025 at 3:43 PM
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! 🤩
March 19, 2025 at 3:43 PM
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.
March 19, 2025 at 3:43 PM
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.
March 19, 2025 at 3:43 PM
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.
Thanks Mimi, so grateful for your mentorship. Cheers to all the collaborations ahead!
February 27, 2025 at 8:45 PM
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! 😊
February 27, 2025 at 4:39 PM
That's so kind of you! Thank you for a brilliant seminar today, and welcome to Uppsala! 😊
Thanks so much, John! 🙏🏻❤️
February 19, 2025 at 9:48 PM
Thanks so much, John! 🙏🏻❤️
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
January 27, 2025 at 10:07 PM
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!
January 27, 2025 at 10:07 PM
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.
January 27, 2025 at 10:07 PM
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.
January 27, 2025 at 10:07 PM
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.
January 27, 2025 at 10:07 PM
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.
January 27, 2025 at 10:07 PM
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.
January 27, 2025 at 10:07 PM
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.
January 27, 2025 at 10:07 PM
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”.
@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”.
January 27, 2025 at 10:07 PM
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”.
@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”.
January 27, 2025 at 10:07 PM
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”.