Giorgio Seano

Amazing job! Well done guys! Funny how conventional therapies enrich for hybrid GBM cells🤩

Giorgio Seano: Why Does Glioblastoma Always Outsmart Treatment? - OncoDaily Giorgio Seano: Why Does Glioblastoma Always Outsmart Treatment? / Adrien Thomas, Alberto Ballestín, cancer, Cathy Pichol-Thievend, Celine Vallot, Curie

Why Does Glioblastoma Always Outsmart Treatment? - Giorgio Seano
@giorgioseano.bsky.social
@institutcurie.bsky.social
@valentino-ribecco.bsky.social
@ggargiul.bsky.social

oncodaily.com/science/glio...

#OncoDaily #Oncology #Cancer #Health #Medicine #MedEd #MedOnc #MedNews #Glioblastoma #NeuroOnc

Proneural-Mesenchymal hybrid glioblastoma cells are resistant to therapy and dependent on nuclear import AbstractBackground. Despite extensive research efforts, glioblastoma (GBM) remains a deadly disease with poor prognosis. Although previous studies have ide

You can dive into all the multi-omics data and findings in the full paper.
Read more: doi.org/10.1093/neuo....
🧵 (9/9)

🌟 Special thanks to @eanoassociation.bsky.social for sharing our work, and heartfelt gratitude to the @erc.europa.eu, @fondationarc.bsky.social @institutcurie.bsky.social and @cnrsbiologie.bsky.social for their generous support. (8/9)

🙏 This research wouldn’t have been possible w/o the work of Oceane Anezo, Jeremy Raymond, Alberto Ballestín, Cathy Pichol-Thievend, Juliette Reveilles, Adrien Thomas, @valentino-ribecco.bsky.social, and the collaboration with Celine Vallot, @ggargiul.bsky.social , Vidhya M. Ravi, Kevin Joseph (7/9)

🎉 Huge congrats to Guillaume Bourmeau, leading author and my brilliant PhD student, for spearheading this work on GBM hybrid cells at @institutcurie.bsky.social! Your dedication made this breakthrough possible. (6/9)
#ProudPI,

🚀 Here's the exciting part: we can target this vulnerability.
We hit them with importazole (import blocker) and selinexor (export inhibitor).
🔥 Targeting nuclear import decreases the hybrid cell pool and enhances chemoradiation sensitivity, opening a new therapeutic avenue against GBM. (5/9)

🛡️ Therefore, these cells are resistant to treatment and are linked to a poorer patient prognosis. Using RNA-seq, nuclear proteome and scChIP-Seq, we discovered their Achilles' heel: a hyperactive nuclear transport system they rely on to import oncogenes like MYC and maintain their state. (4/9)

a cartoon drawing of a person holding a pencil with a lightning bolt around it ALT: a cartoon drawing of a person holding a pencil with a lightning bolt around it

🤯 These hybrid cells don’t just look different, they proliferate like they’re on Red Bull and shrug off DNA damage after irradiation. Have they got superhuman repair skills? 🙄 (3/9)

a man is peeking through a doorway and smiling . ALT: a man is peeking through a doorway and smiling .

🔬 Using dual fluorescent reporters for proneural & mesenchymal states, we tracked live patient-derived glioblastoma lines and uncovered a hybrid population expressing both signatures... let's talk about an identity crisis! (2/9)

Background: Despite extensive research efforts, glioblastoma (GBM) remains a deadly disease with poor prognosis. Although previous studies have identified various cell states within GBM tumors, the molecular mechanism underlying adaptive GBM cell plasticity induced by conventional therapy remains unclear. Methods: We used fluorescent reporters for proneural (PN) and mesenchymal (MES) subtypes to monitor GBM cell plasticity in real-time across multiple patient-derived cell lines. This approach revealed cells that concurrently expressed both proneural and mesenchymal markers. To investigate this unique hybrid population, we implemented a comprehensive methodological approach encompassing bulk and single-cell RNA sequencing, single-cell ChIP sequencing, nuclear proteomics, high-resolution imaging, orthotopic mouse models, clinical dataset analysis, and pharmacological and genetic techniques. This multifaceted strategy allowed us to gain functional and molecular insights into this distinct cellular population. Results: We showed that these hybrid cells are increased by conventional therapies, and are resistant to these therapies. At the molecular level, hybrid cells display significant alterations in chromatin structure and nuclear protein composition, elevated transcriptional activity, Myc activation, and improved transport between the nucleus and cytoplasm. Genetic and pharmaceutical inhibition of the nuclear import/export shuttling machinery, increased in hybrid cells, effectively suppressed adaptive GBM cell plasticity and hybrid identity, thereby enhancing the sensitivity of GBM cells to therapies. Conclusion: Our results indicate that GBM hybrid cells play a crucial role in chemoradiation resistance. The nuclear transport machinery presents a potential therapeutic target for hybrid cells, offering a way to counteract the typical resistance to treatment observed in GBM.

🧠 Why does glioblastoma always outsmart treatment? In our #Neuro-Oncology paper, we identified proneural-mesenchymal hybrid glioblastoma cells that are resistant to therapy and dependent on nuclear import. doi.org/10.1093/neuo...
Short walkthrough below. Let’s dive in! 🧵 (1/9)
#GBM, #BrainTumor

Academic Podcasts for Researchers & Scientists Looking for the best academic podcasts? I have recommendations for academic writing podcasts, podcasts for PhD students and other podcasts on academia – from leadership and academic life to teaching.

🎧 I made this list in 2021, but these podcasts are still in my rotation!

If you're a researcher looking for relevant and useful information for academics, check out these top podcast suggestions and learn something new this week. -> https://rpst.page.link/rxCs

#AcademicWriting #PhDSky #PhDchat

📣 Have you heard? Registration for #EANO2025, taking place Oct 16-19, 2025 in #Prague (CZ) is open! Don’t miss out on this fantastic experience to meet experts in the field of #NeuroOncology. Early Bird fees available until July 31, 2025. 👉 eano.eu/eano2025/reg... #braincancer #medsky

Congratulations to the 2025 Cancer Discovery Early Career Award winner: Sandra Misale! @sandramisale.bsky.social #AACR25

Well deserved!! Congrats Dr. Jain!!

The AACR congratulates Rakesh K. Jain, PhD, FAACR, who will be honored with the 2025 AACR Award for Lifetime Achievement in Cancer Research at #AACR25. www.aacr.org/about-the-aa... #AACRFellows @harvardmed.bsky.social

📢 Call for Applications
EANO & @neuroonc.bsky.social are seeking a new Editor-in-Chief for Neuro-Oncology Advances!

✅ Strong background in #NeuroOncology
✅ Editorial leadership experience

🗓️ Deadline: May 31, 2025
🔗 More info: bit.ly/4j9AqV7

#EANO #SNO #NeuroOncologyAdvances #CallForApplications

Methylation-Based Deconvolution Unveils Glioblastoma Heterogeneity and Cell-Type Composition Linked to Patient Survival https://www.biorxiv.org/content/10.1101/2025.02.27.640603v1

Congrats @thomasdaubon.bsky.social... Cool story!!

Of course! Done…

A new paper on microplastics accumulating in the brain was just published in Nature Medicine. I've reviewed the background and main findings in a new Ground Truths post erictopol.substack.com/p/the-microp...

SAVE THE DATE: Brain Tumor Microenvironment Symposium, 30th & 31st January 2025, Paris - Siric Cancer - Curamus - Site de Recherche Intégrée sur le Cancer Dans le cadre de son programme de recherche intégrée « Cerveau, cancer et immunité – dialogue cellulaire dans les tumeurs cérébrales », […]

Looking forward to meeting a lot of good international and French friends at the Brain Tumor Microenvironment Symposium organized by the Institut du Cerveau... Super cool lineup!! #GBM #TME
curamus-cancer.fr/brain-tumor-...

Glioblastoma drives protease-independent extracellular matrix invasion of microglia Glioblastoma (GBM) is the most common and lethal form of primary brain cancer. Microglia infiltration into the tumor microenvironment is associated wi…

Wanted to stat today with some new #harleylab science.

ChiaWen Chang is leading efforts to understand immune cell patterning in the brain in glioblastoma. He started w/ the inverse question: how do GBM cells influence microglia (brain-resident immune cells)?

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

Sure, done!!

Sure!! You’re in!!

👍

You’re in now!!

Welcome in!!

H4K20me3-Mediated Repression of Inflammatory Genes Is a Characteristic and Targetable Vulnerability of Persister Cancer Cells Cell persistence and senescence are distinct states of proliferative arrest induced by cancer therapy, with persister cells being characterized by the silencing of inflammatory genes through the heter...

I am thrilled to finally share our work on persister cancer cells: we identify distinctive features and actionable #vulnerabilities ⚡️of persister cancer cells (#DTP), and provide mechanistic insight into their low #inflammatory activity:
aacrjournals.org/cancerres/ar...

A foundation model of transcription across human cell types - Nature A foundation model learns transcriptional regulatory syntax from chromatin accessibility and sequence data across a range of cell types to predict gene expression and transcription factor interactions...

A new large language of life model (LLLM) for the transcriptome that predicts gene expression within and across human cell types www.nature.com/articles/s41... @nature.com
For more on the remarkable surge of LLLMs see erictopol.substack.com/p/learning-t...