iiinova — where your digital self keeps evolving

Slim Mzoughi @sleemmz.bsky.social · 13/07/2026

🔬 Come build something new with us in NYC 🗽. We're hiring a Postdoctoral Fellow and an Assistant Scientist at Mount Sinai. We study functional heterogeneity, cell-state plasticity, and tumor evolution, and we're looking for curious, ambitious scientists ready to tackle bold questions. Please share!

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Slim Mzoughi @sleemmz.bsky.social · 25/06/2025

📢 Exciting news: The Mzoughi Lab will launch in January 2026 at the Icahn School of Medicine at Mount Sinai in NYC! Young talents and cell plasticity enthusiasts—stay tuned for upcoming opportunities!

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Slim Mzoughi @sleemmz.bsky.social · 12/02/2025

About the cover: The mutant intestinal epithelium (jar) generates diverse CSC flavors (gummies): canonical LGR5+(orange), non-canonical oncofetal (blue), and a spectrum of intermediate states. This CSC heterogeneity fuels CRC progression and underpins its ability to evade therapy.

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Slim Mzoughi @sleemmz.bsky.social · 12/02/2025

🔈We've got the cover of the 2nd NG issue for 2025🙌 Read about the cover: In the comment👇 Also check out our research briefing🚨 (link below): nature.com/articles/s41... nature.com/articles/s41...

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Slim Mzoughi @sleemmz.bsky.social · 11/02/2025

Key takeaways can be found in this thread: bsky.app/profile/slee...

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Slim Mzoughi @sleemmz.bsky.social · 11/02/2025

Thanks, Chris. More info in this thread: bsky.app/profile/slee...

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Chris Tape @christophertape.bsky.social · 11/02/2025

Nice paper from @sleemmz.bsky.social et al underscoring the importance of stem cell transdetermination in CRC. RXR, YAP, and AP1 signalling collectively control access to revival stem cells and inhibition of these nodes limits plasticity to improve chemosensitivity. www.nature.com/articles/s41...

nature.com

Oncofetal reprogramming drives phenotypic plasticity in WNT-dependent colorectal cancer - Nature Genetics

Oncofetal (OnF) reprogramming, driven by YAP and AP-1, induces phenotypic plasticity and therapy resistance in WNT-dependent colorectal cancer (CRC). Targeting the OnF state in combination with chemot...

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Slim Mzoughi @sleemmz.bsky.social · 10/02/2025

Thank you, Chris, for all your support!

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Chris Marine Lab @marinelab.bsky.social · 10/02/2025

So happy to see this live, Slim! Congratulations to you, Ernesto and the whole team for your resilience, vision and creativity!

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Slim Mzoughi @sleemmz.bsky.social · 10/02/2025

10b) A2. Resistance. The OnF state is inherently resistant to FOLFIRI. We believe LGR5+ cells must activate this program to survive treatment. Targeting the OnF state (genetically) or its drivers (pharmacologically) improves the effectiveness and durability of current chemotherapies.

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Slim Mzoughi @sleemmz.bsky.social · 10/02/2025

10) Q: What role do OnF cells play? A1: Tumor growth. The canonical LGR5+ and non-canonical OnF CSCs work in tandem to drive tumor growth. Targeting either state alone is insufficient- they are functionally redundant in this context.

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Slim Mzoughi @sleemmz.bsky.social · 10/02/2025

9) Q: How are YAP and AP-1 activated? A: RXR acts as a gatekeeper of the OnF program. Its deregulation following APC LoF activates YAP/AP-1 and establishes an OnF memory, sustained by these TFs during disease progression. RXR is critical during tumor initiation but not in advanced CRC

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Slim Mzoughi @sleemmz.bsky.social · 10/02/2025

8) Q: What drives the OnF program? A: YAP and AP-1 cooperate but play distinct roles in driving OnF reprogramming. YAP triggers the program at tumor onset, partially by activating AP-1. But Subsequent AP-1 hyperactivation during disease progression breaks lineage-restrictive barriers.

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Slim Mzoughi @sleemmz.bsky.social · 10/02/2025

7) Q: Why does it occur? A: OnF reprogramming of mutant LGR5+ SCs creates a continuum of phenotypes delimited by the canonical LGR5+ and non-canonical OnF states–a phenotypic heterogeneity key to primary resistance. Cells at the extreme OnF end exhibit lineage infidelity/plasticity.

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Slim Mzoughi @sleemmz.bsky.social · 10/02/2025

6) Q: Is fetal-like reprogramming transient in CRC, like in injury? A: Oncofetal (OnF) reprogramming of intestinal stem cells (ISCs) is triggered by APC LoF during tumor initiation and persists in advanced tumors. KRASG12D and p53 LoF favor the OnF and LGR5+ states, respectively.

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Slim Mzoughi @sleemmz.bsky.social · 10/02/2025

5) Takeaways: 6.Diverse flavors/states of CSCs exist in CRC. 7. The OnF state is inherently resistant to therapies and is co-opted by some LGR5+ CSCs to survive treatment. 8. The success and durability of current CRC therapies hinges on effective targeting of the OnF program.

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Slim Mzoughi @sleemmz.bsky.social · 10/02/2025

5) Takeaways: 6. Diverse flavors/states of CSCs exist in CRC. 7. The OnF state is inherently resistant to therapies and is co-opted by some LGR5+ CSCs to survive treatment. 8. The success and durability of current CRC therapies hinges on effective targeting of the OnF program.

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Slim Mzoughi @sleemmz.bsky.social · 10/02/2025

3) Takeaways: 1. OnF reprogramming of mutant LGR5+ SCs triggers phenotypic (intratumoral) heterogeneity during tumor initiation and drives lineage plasticity in advanced CRC. 2. While YAP initiates the OnF program, subsequent AP-1 hyperactivation drives lineage plasticity.

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Slim Mzoughi @sleemmz.bsky.social · 10/02/2025

2) Longstanding Q: Why is targeting LGR5+ CSCs insufficient for achieving better therapeutic outcomes? A: 1. The OnF state can sustain tumor growth in absence of the LGR5+ CSCs. 2. The LGR5+ state is sensitive to current therapies. Resistance is primarily driven by the OnF program.

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Slim Mzoughi @sleemmz.bsky.social · 10/02/2025

Thrilled to share my 1st brainchild, out today @naturegenet.bsky.social 🚀 Been hearing a lot about fetal-like states lately? We uncover the molecular mechanisms, functional significance and clinical relevance of #oncofetal reprogramming in CRC. www.nature.com/articles/s41... (rdcu.be/d9iSN) a 🧵

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Slim Mzoughi @sleemmz.bsky.social · 08/12/2024

could you pls add me. Thanks.

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Nature Portfolio @natureportfolio.nature.com · 26/11/2024

The Human Cell Atlas is yielding detailed maps of human tissues and systems throughout life, along with methods to handle single-cell data. Four scientists reflect in Nature on how the project is transforming our understanding of human biology. 🧪

go.nature.com

Cellular atlases are unlocking the mysteries of the human body

Scientists reflect on insights from the Human Cell Atlas.

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Slim Mzoughi @sleemmz.bsky.social · 24/11/2024

Duncan, i'd love to join. thanks.

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Eslam Katab @eslamkatab.bsky.social · 23/11/2024

A shared meal, a kiss on the cheek: these social acts bring people together — and bring their microbiomes together, too. …. It is fascinating how our microbiome is shaped! www.nature.com/articles/d41...

nature.com

Your friends shape your microbiome — and so do their friends

Analysis of nearly 2,000 people living in remote villages in Honduras reveals who’s spreading gut microorganisms to whom.

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Slim Mzoughi @sleemmz.bsky.social · 20/11/2024

Happy with the move to🦋 ! I hope we can use this platform as a fresh start to foster meaningful scientific discussions and collegiality, rather than superficial praise or unproductive disagreements.

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Slim Mzoughi @sleemmz.bsky.social · 19/11/2024

i'd love to be added. Thanks.

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Slim Mzoughi @sleemmz.bsky.social · 19/11/2024

Johanna, can you please add me? thanks.

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