Marton Olbei

Decoding cytokine networks in ulcerative colitis to identify pathogenic mechanisms and therapeutic targets Systems immunology reveals how cytokine-cytokine signaling is dysregulated in an inflammatory bowel disease.

www.science.org/doi/10.1126/...

Decoding cellular conversations in ulcerative colitis reveals new drug targets New research reveals previously hidden mechanisms driving inflammation and identifies new therapeutic targets, including some already showing success...

www.imperial.ac.uk/news/article...
Summary of our recent publication on cytokine networks in ulcerative colitis

Decoding cytokine networks in ulcerative colitis to identify pathogenic mechanisms and therapeutic targets Systems immunology reveals how cytokine-cytokine signaling is dysregulated in an inflammatory bowel disease.

Through systems immunology analysis, a team has identified potential therapeutic targets for the treatment of #UlcerativeColitis, an inflammatory bowel disease characterized by dysregulated cytokine signaling in the GI tract. #ScienceSignaling https://scim.ag/4cdvxdv

Huge thanks to our collaborators and the patients who donated samples making this research possible! 🙏

#ScienceSignalingResearch #Immunology #IBD #UlcerativeColitis #SystemsBiology

Beyond UC, this methodology can be applied to other immune-mediated inflammatory diseases (IMIDs) to reveal cytokine network dynamics and potentially highlight novel therapeutic targets.

TL1A emerged as an upstream regulator of both TNF and IL-23A. Since drugs already target those downstream cytokines, TL1A is a promising target that could disrupt multiple inflammatory pathways simultaneously.

Several cytokines showed altered interactions across disease states: IL-22, TL1A, IL-23A, and OSM. We also predicted which JAK family members mediate specific cytokine-cytokine interactions.

Network plot depicting interactions unique to treatment naive UC samples, making up 19% of total interactions in the network

We discovered a cytokine subnetwork unique to treatment-naive UC patients, the inflammatory landscape changes once treatment begins.

Schematic figure representing ILC1 cells signalling throufg IFNG, TNF and TGFB1 to patient derived organoid models, and the cytokines responding to them in turn

To validate our predictions, we used patient-derived colonic organoids and organoid-ILC cocultures to test whether predicted cytokine-cytokine interactions actually occur in a physiologically relevant system.

A pipeline figure depicting how single-cell RNA-Seq data was processed to model cytokine interactions

We used systems immunology to analyse single-cell RNA-seq data from colonic biopsies of treatment-naive patients, treatment-exposed patients, and healthy donors, building cytokine interaction networks across disease states.

A small interaction network depciting TL1A regulating downstream cytokines, including TNF and IL-23

Our findings reveal how the cytokine network gets "rewired" in UC and highlights TL1A as a key upstream regulator of TNF and IL-23A, cytokines already targeted by approved drugs. This could inform therapeutic strategies.

Decoding cytokine networks in ulcerative colitis to identify pathogenic mechanisms and therapeutic targets Systems immunology reveals how cytokine-cytokine signaling is dysregulated in an inflammatory bowel disease.

Why do many UC patients struggle despite cutting-edge biologics? We suspected the answer lies not in individual cytokines, but in how they communicate as an interconnected network during disease and treatment. Our new
KorcsmarosLab paper published in Science Signaling
www.science.org/doi/10.1126/...

Systems immunology reveals how cytokine-cytokine signaling is dysregulated in an inflammatory bowel disease @martonolbei.bsky.social @imperialcollegeldn.bsky.social
www.science.org/doi/10.1126/...

🥁 Check out our new preprint on OmniPath, the prior knowledge resource for #SystemsBiology, and its brand-new OmniPath Explorer web app! 🥳

📖 Preprint: www.biorxiv.org/content/10.1...
🔍 Explorer: explore.omnipathdb.org

OmniPath integrates 160+ resources for multi-omics analysis & modeling.

🧶⬇️

Excited to share that I started a new chapter in my career as a Teaching Fellow at Imperial College London! I really enjoy teaching, and look forward to the opportunities and challenges ahead.

📄 Update on our preprint about Gene Regulatory Net (GRN) benchmarking 📄
We have included the original and decoupled version of SCENIC+, added a new metric and two more databases. Dictys and SCENIC+ outperformed others, but still performed poorly in causal mechanistic tasks.
doi.org/10.1101/2024... 👇

Decoding Cytokine Networks in Ulcerative Colitis to Identify Pathogenic Mechanisms and Therapeutic Targets Ulcerative colitis (UC) is a chronic inflammatory disorder of the gastrointestinal tract characterised by dysregulated cytokine signalling. Despite the advent of advanced therapies targeting cytokine ...

Excited to share our work on UC cytokine networks at #ECCO2025.
Come by poster P0104 if you are interested in:
- how cytokines regulate each other in UC
- the role of TL1A in treatment-naive UC
- how we could use this approach to identify new drug targets
www.biorxiv.org/content/10.1...

We present NetworkCommons, a unified platform 🪐 for network biology, providing access to omics data, knowledge, and contextualization methods, all with a consistent API 👇🧵
Paper: doi.org/10.1101/2024...
Docs: networkcommons.readthedocs.io