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Reposted by Grünewald Lab

Kilian Schober @kischober.bsky.social · 3d

German press release: www.uk-erlangen.de/presse/press...

Wie das Immunsystem seine Abwehrtruppen auswählt

Wenn Killerzellen des Immunsystems auf Anzeichen einer Infektion stoßen, teilen sich manche von ihnen danach rasant. Sie wachsen so zu einer großen Abwehrtruppe heran, die dann den Erreger bekämpft. A...

www.uk-erlangen.de

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Reposted by Grünewald Lab

Kilian Schober @kischober.bsky.social · 5d

If the immune system is an army...
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would you rather rely on one “super warrior” — or on a diverse team of fighters, even if none of them is the single strongest?

I’d go with the team.

Why? Check out our new study, just published in Science Immunology: www.science.org/doi/10.1126/...

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Reposted by Grünewald Lab

Elizabeth McKenna @elizsmckenna.bsky.social · 5d

Now online in Cancer Discovery @aacrjournals.bsky.social: Epigenetic and Transcriptional Programs Define #Osteosarcoma Subtypes and Establish Targetable Vulnerabilities - by Eunice López-Fuentes, Alejandro Sweet-Cordero, and colleagues doi.org/10.1158/2159... @ucsfchildrens.bsky.social

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Grünewald Lab @grunewaldlab.bsky.social · 10d

New review in JCO Precision Oncology by the NEWTS group of the @euroewing.bsky.social consortium:

Recurrent and Refractory Ewing #Sarcoma Phase I/II Trials: Current Perspective From the Euro-Ewing Consortium

ascopubs.org/doi/10.1200/...

International collaboration is KEY for clinical trials!

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Grünewald Lab @grunewaldlab.bsky.social · 10d

www.sciencedirect.com/science/arti...

Refined culture conditions with increased physiological relevance uncover oncogene-dependent metabolic signatures in Ewing sarcoma spheroids

Ewing sarcoma (EwS) cell line culture largely relies on standard techniques, which do not recapitulate physiological conditions. Here, we report on a …

www.sciencedirect.com

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Grünewald Lab @grunewaldlab.bsky.social · 11d

A Vascularized Microphysiological System Reproducing Endochondral Ossification in Vitro to Study Ewing #Sarcoma Proliferation and Migration

advanced.onlinelibrary.wiley.com/doi/full/10....

A Vascularized Microphysiological System Reproducing Endochondral Ossification in Vitro to Study Ewing Sarcoma Proliferation and Migration

A biofabricated 3D in vitro model recapitulating endochondral ossification (ECO) is described, mimicking the steps from condensation to chondrogenesis and hypertrophy, culminating with vascularizatio...

advanced.onlinelibrary.wiley.com

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Grünewald Lab @grunewaldlab.bsky.social · 13d

New cell lines expanding the diversity of
#Ewing #sarcoma models

onlinelibrary.wiley.com/doi/10.1002/...

New cell lines expanding the diversity of Ewing sarcoma models

A chromosomal translocation between the EWSR1 and ETS genes is the key oncogenic driver in Ewing sarcoma. EWSR1::FLI1, the most frequent fusion, is subdivided into different fusion types with unclear...

onlinelibrary.wiley.com

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Grünewald Lab @grunewaldlab.bsky.social · 14d

Very proud on our stellar doctoral student, Maxim Kafka, for being awarded with a Mildred-Scheel doctoral scholarship from the German Cancer Aid.

Maxim is working @dkfz.bsky.social on a follow-up on our recent paper on #SMARCB1-deficient Epitheloid #Sarcoma

onlinelibrary.wiley.com/doi/10.1002/...

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Reposted by Grünewald Lab

David Meyer @meyerdh.bsky.social · 21d

🕰️ Is aging driven by a programmed/programmatic mechanism, or by the unavoidable burden of imperfect maintenance? Our perspective argues that aging reflects finite maintenance and reduced evolutionary pressure🧵🧪 www.nature.com/articles/s43... @bjornschumacher.bsky.social @alexeimaklakov.bsky.social

Aging by the clock and yet without a program - Nature Aging

Meyer and colleagues refute the idea that, as aging can be tracked precisely by clocks, it must be driven by a biological program. They propose that imperfect maintenance and repair processes resultin...

www.nature.com

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Reposted by Grünewald Lab

Fendt Lab @fendtlab.bsky.social · Sep 5

Big congratulations to @elialab.bsky.social who is an alumni of the lab! So well deserved!

Ilaria Elia @elialab.bsky.social · Sep 5

I am thrilled to share that I have received an ERC Starting Grant for our project SpaceMet!
I am grateful for the ERC’s commitment to ambitious early-stage research and to KU Leuven for their support!
Stay tuned, new postdoc positions coming soon!I @erc.europa.eu @kuleuvenuniversity.bsky.social

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Reposted by Grünewald Lab

Wolfgang Wick @wickwolfgang.bsky.social · Sep 8

NOA Researchers from 13 German sites led by a team from @uniheidelberg.bsky.social @Universitätsklinikum Heidelberg (UKHD) & @dkfz.bsky.social have successfully completed the multicenter study “NCT Neuro Master Match (N2M2)”.

Molecularly matched targeted therapies plus radiotherapy in glioblastoma: the phase 1/2a N2M2 umbrella trial

Nature Medicine - In a phase 1/2a umbrella trial in patients with glioblastoma matching targeted therapies according to tumor molecular profiling, temsirolimus plus radiotherapy improved PFS...

rdcu.be

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Reposted by Grünewald Lab

Kurianlab @kurianlab.bsky.social · Sep 8

Many conserved exons in the heart and brain utilize weak 5 ′ splice sites, yet they are accurately spliced. But how? We show that splicing fidelity is actively enforced through a QKI-U6 checkpoint at the U1→U6 handover in essential cardiac genes during organogenesis.
www.biorxiv.org/content/10.1...

QKI ensures splicing fidelity during cardiogenesis by engaging the U6 tri-snRNP to activate splicing at weak 5ʹ splice sites

During organogenesis, precise pre-mRNA splicing is essential to assemble tissue architecture. Many developmentally essential exons bear weak 5'splice sites (5'SS) yet are spliced with high precision, ...

www.biorxiv.org

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Grünewald Lab @grunewaldlab.bsky.social · Sep 8

Great new perperint by Leo Kurian and team!

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Grünewald Lab @grunewaldlab.bsky.social · Sep 4

We are very grateful to our patients, and for generous funding of this project by the German Cancer Aid, the DKTK, and the Boehringer-Ingelheim Foundation!

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Grünewald Lab @grunewaldlab.bsky.social · Sep 4

This project was a true #team effort and great collaboration of @dkfz.bsky.social @uniheidelberg.bsky.social @nct-heidelberg.bsky.social @institutcurie.bsky.social and the Balgrist University Hospital.

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Grünewald Lab @grunewaldlab.bsky.social · Sep 4

These findings reveal a mechanistic link between oncogene fluctuation, amino acid metabolism, and immune evasion, positioning AHR as a central mediator of EwS progression and a tractable therapeutic vulnerability.

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Grünewald Lab @grunewaldlab.bsky.social · Sep 4

Functionally, AHR silencing restores NK cell-mediated tumor recognition, while also directly suppressing EwS cell proliferation, clonogenicity, and spheroid growth in plasma-like media. Genetic inhibition of AHR reduces tumor burden and metastatic competence in xenograft models.

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Grünewald Lab @grunewaldlab.bsky.social · Sep 4

Low EWSR1::ETS states foster tryptophan catabolism and accumulation of the AHR agonist kynurenine, which in turn promotes an immunosuppressive tumor microenvironment characterized by impaired natural killer (NK) cell cytotoxicity and enrichment of immunoregulatory infiltrates.

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Grünewald Lab @grunewaldlab.bsky.social · Sep 4

Here, by employing an integrative functional metabolomics approach, we link reduced EWSR1::ETS activity in primary EwS tumors to adverse clinical outcome and pronounced activation of the aryl hydrocarbon receptor (AHR) pathway.

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Grünewald Lab @grunewaldlab.bsky.social · Sep 4

Ewing sarcoma (EwS), driven by EWSR1::ETS fusion transcription factors, constitutes an ideal model to interrogate this question, as fluctuations in fusion activity direct divergent transcriptional programs.

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Grünewald Lab @grunewaldlab.bsky.social · Sep 4

The extent to which dynamic changes in #oncogene activity shape cancer cell #metabolism and drive disease progression remains poorly understood.

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Grünewald Lab @grunewaldlab.bsky.social · Sep 4

Check out our updated preprint!

Using functional #metabolomics, we link reduced EWSR1::ETS activity in Ewing #sarcoma to poor outcome and activation of the AHR pathway, which promotes immune evasion characterized by impaired NK cell function and immunoregulatory infiltrates.

tinyurl.com/2b6cry3m

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Reposted by Grünewald Lab

Soragni:Lab @alice.soragnilab.com · Aug 26

Big day for our team: our pheochromocytoma and paraganglioma (PPGL) organoid paper is now up on bioRxiv!

This was a tour de force across 6 institutions, 37 authors, building patient-derived organoids from 35 PPGL patients /🧵

🔗 www.biorxiv.org/content/10.1...

Patient-derived organoids reveal hypoxia-driven plasticity and therapeutic vulnerabilities in pheochromocytomas and paragangliomas

Pheochromocytomas and paragangliomas (PPGLs) are rare chromaffin cell-derived neuroendocrine tumors of sympathetic (catecholamine-producing) or parasympathetic (nonsecretory) origin, frequently driven...

www.biorxiv.org

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Grünewald Lab @grunewaldlab.bsky.social · Aug 26

High content-imaging drug synergy screening identifies specific senescence-related vulnerabilities of mesenchymal neuroblastomas

www.nature.com/articles/s41...

High content-imaging drug synergy screening identifies specific senescence-related vulnerabilities of mesenchymal neuroblastomas - Cell Death & Disease

Cell Death & Disease - High content-imaging drug synergy screening identifies specific senescence-related vulnerabilities of mesenchymal neuroblastomas

www.nature.com

Grünewald Lab @grunewaldlab.bsky.social · Aug 23

Great back-to-back papers in @natcomms.nature.com
tinyurl.com/3dp98bke
tinyurl.com/wy9ychb2
on MCL1 as a novel therapeutic target in CIC::DUX #sarcomas

These cancers remain challenging (tinyurl.com/kz4h8rws) but these studies spark hope! Glad that our division @dkfz.bsky.social could contribute!

Patient-derived tumoroids from CIC::DUX4 rearranged sarcoma identify MCL1 as a therapeutic target - Nature Communications

Despite their differences, the rarer sarcoma CIC::DUX4 sarcoma (CDS) is typically treated with therapies developed for Ewing Sarcoma (EwS) with limited success. Here, the authors develop a co-clinical...

tinyurl.com

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