Srustidhar Das

How liver X receptor regulates intestinal regeneration and tumor growth Click to launch & play an online audio visual presentation by Dr. Srustidhar Das on How liver X receptor regulates intestinal regeneration and tumor growth, part of a collection of multimedia lectures...

🎧 Excited to share my Henry Stewart Talks (#HSTalks) interview on our recent @natureportfolio.nature.com paper — showing how liver X receptor (LXR) acts as a molecular “rheostat,” boosting intestinal repair while restraining tumor growth.

👉 Take a listen here: doi.org/10.69645/QUT...

Fantastic work, huge congratulations @katajistolab.bsky.social !!!

Thank you @ianlmorgan.bsky.social !!!

Finally thrilled to share this - my first real attempt at #SciComm! 🎉
Grateful to the amazing @investnscience.bsky.social team for organizing a fantastic workshop, providing the platform, editing support, and most importantly, encouraging critical thinking to simplify the message. Thank you!!!

IL-33-activated ILC2s induce tertiary lymphoid structures in pancreatic cancer - Nature IL-33 induces tertiary lymphoid structures.

Fascinating new @natureportfolio.bsky.social study from @thevinodlab.bsky.social @mskcancercenter.bsky.social:IL33, an alarmin from inflamed tissues, drives ILC2 migration from the gut to the pancreas, forming TLS with anti-tumor effects in PDAC. www.nature.com/articles/s41...

We just can't stop recruiting!

Associate professor in cell and molecular biology @dunnschool, with a preference for immunology, inflammation and/or infection - all defined broadly

Come and be our colleague

Deadline 28 Feb, please spread the word

www.path.ox.ac.uk/vacancy/asso...

Healing limited Activation of liver X receptor promotes tissue regeneration over neoplastic transformation.

Big thanks to Amy E. Baek for spotlighting our recently published work in Nature @nature.com in the Editor's Choice section of @ScienceSignaling @science.org! www.science.org/doi/10.1126/...

Can I also join please!!!

The Liver X Receptor Axis Balances Intestinal Regeneration and Tumorigenesis Major Finding: The liver X receptor (LXR) pathway drives intestinal regeneration and limits tumorigenesis.Concept: Transcriptomic and pharmacologic studies define a CYP27A1–LXR–TLS signaling axis in i...

Thanks Cancer Discovery Journal, @AACR for highlighting our recently published work @natureportfolio.bsky.social!!! The Liver X Receptor Axis Balances Intestinal Regeneration and Tumorigenesis doi.org/10.1158/2159....

Thanks Annika!!!

An epithelial adaptation mechanism to damage, whereby LXR functions as a rheostat, promoting tissue repair while limiting tumorigenesis @ejvillablanca.bsky.social @srudas.bsky.social
nature.com/articles/s41...

On a personal note - this work was a labor of love spanning over 7 years. I’m now on the #jobmarket, looking to start my own group and further explore how tissue homeostasis is maintained in the gut and beyond.
Would love to hear about any potential opportunity! #newbeginning

Grateful to our funders— @Cancerfonden @Åke Weibergs Stiftelse @FormasForsk @Vetenskapsradet @ERC_Research @Wstiftelserna @reNEW_Global
@EUbOPEN - for making this work possible!

Thank you @ barbmarte.bsky.social @ natureportfolio.bsky.social, and our fantastic reviewers who helped shape the paper into its final form.

A heartfelt thanks to @ ejvillablanca.bsky.social @ karolinskainst.bsky.social, for the trust, freedom to challenge the status quo, and unwavering support throughout this long journey! 🙌✨

A huge shoutout to all co-authors, especially@martinaparigi.bsky.social and@xinxinluo.bsky.social-two amazing colleagues and co-first authors I had the privilege to work with - and to all our collaborators. Special thanks to@katajistolab.bsky.social for teaching us the art of growing #organoids! 🙌✨

We uncovered a pathway that unlinks #regeneration and #tumorigenesis – a discovery with profound implications for #regenerativemedicine. This holds promise for #IBD, #cancer, and beyond!

Next, we explored how is LXR activated endogenously. Revisiting our #transcriptomics datasets from damage-repair models, we uncovered a key player: #CYP27A1, a cholesterol-metabolizing enzyme. It’s induced by damage and acts upstream of LXR – a critical piece of the puzzle!

How does LXR activation inhibit tumorigenesis?
Using longitudinal #bulk & #spatialtranscriptomics, we found LXR bolsters adaptive immunity - supporting B cells & CD8+ T cells to suppress tumor growth.

Interestingly, during tumorigenesis, LXR activation doesn’t induce AREG or similar EGFR ligands. Something to explore in the future! 🤔

How does LXR promote regeneration?🤔
Using #scRNAseq and #organoids, we found that LXR induces amphiregulin – an EGFR ligand – in epithelial cells (previously understudied cellular source), to promote regeneration, and was validated with AREG KO mice and neutralizing antibody.

Does it increase tumor risk? 🤔
Unlike other pro-regenerative modulators, LXR activation inhibited tumorigenesis – an #unlinker of #regeneration and #tumorigenesis!

Using #invivo gain and loss-of-function studies and #invitro #organoids, we showed that LXR activation in intestinal epithelial cells (IECs) promotes intestinal regeneration.

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Previous studies have shown the anti-tumor potential of LXR: but could it hold the key to #unlinking #regeneration from #tumorigenesis? We wanted to find out.

We analyzed #transcriptomics datasets from two intestinal regeneration models #DSS and #irradiation and identified a key player: the #LXR pathway.
Activated in response to damage, it hinted at a potential role in promoting regeneration –a function that has not been explored before.

a young boy is balancing a bowl on his head . ALT: a young boy is balancing a bowl on his head .

However, #regeneration is invariably linked to #tumorigenesis. With #IBD patients at higher risk for colorectal cancer #CRC, we asked: can regeneration be uncoupled from tumorigenesis? The gut, with its remarkable regenerative capacity, was the perfect model to explore this.

a man with a beard is sitting with his eyes closed and the word thinking is above him ALT: a man with a beard is sitting with his eyes closed and the word thinking is above him

Why #gut?
Being in an #IBD lab made it obvious, but two reasons guided our question:
~35–50% of IBD patients fail or relapse despite advancements in biologics.
Mucosal healing improves outcomes – a critical unmet need!
Can we promote #regeneration to achieve better outcomes?

Do you wonder if #regeneration and #tumorigenesis are always linked, or can they be unlinked to maintain tissue homeostasis? 🤔
Excited to share our latest work published in @Nature, where we explore this fundamental question in the #gut!
Link: www.nature.com/articles/s41... 🧵👇