On April 3rd, 2025, Sonia Aristin successfully defended her PhD thesis entitled “Transcriptional diversity of regulatory T (Treg) cells in colorectal cancer.” Sonia’s research has provided important new insights into how T cells and colorectal cancer (CRC) tumors interact, using innovative in vitro and in vivo models. Her work demonstrates that CRC tumor-derived organoids can directly influence T cell differentiation, promoting the development of immunosuppressive regulatory T cells. Strikingly, she also showed that CRC tumors can systemically affect Treg cell identity in vivo. It has been an real pleasure to work with Sonia during her PhD journey. I’m very proud of her achievements and excited to see where her career will take her next!
A BIG thank you as well to the rest of the supervisory team—Onno Kranenburg, Stefan Prekovic, and Enric Mocholi—and importantly to Worldwide Cancer Research for funding this important fundamental work.
Grant: Integrating Metabolism and Signaling in the Control of Somitogenesis
In a new collaboration with Ina Sonnen (Hubrecht Institute) and Marianne Bauer (TU/Delft), we have recently secured funding to investigate the interplay between metabolic regulation and signaling dynamics during mammalian somitogenesis. While the role of canonical pathways such as Wnt, Notch, and FGF in presomitic mesoderm (PSM) patterning is well established, emerging evidence points to metabolic activity—particularly glycolysis—as a critical, yet underexplored, modulator of this process.
Our preliminary data demonstrate spatially resolved glycolytic gradients and dynamic acetyl-CoA production along the PSM, coinciding with transcriptional transitions and segmentation clock activity. Intriguingly, we have identified nuclear-localized glycolytic and acetyl-CoA-generating enzymes—including PDHc and ACLY—as differentially expressed and, in some cases, oscillatory in nature. This suggests a potential role for metabolic enzymes in modulating chromatin accessibility and transcriptional states in a temporally controlled manner.
Our project will explore how spatiotemporal metabolic flux integrates with signaling to regulate cell fate transitions during somite formation. By dissecting the functional contribution of nuclear metabolic activity to transcriptional regulation and epigenetic remodeling, we aim to uncover new mechanistic insights into vertebrate axis formation and congenital segmentation defects.
Many thanks to ZonMW for submitting this fundamental research.
Paper: Powering Inflammation. How T Cell Metabolism Shapes Gene Expression in Juvenile Arthritis
Our latest study reveals a critical link between cellular metabolism and gene regulation in Juvenile Idiopathic Arthritis (JIA). Enric Mocholi found that activated CD4+ T cells in JIA patients undergo a metabolic shift towards glycolysis, directly influencing histone acetylation and gene expression, fueling inflammation.
Key Findings:
- JIA CD4+ T cells show increased glycolysis, driving disease-specific H3K27ac histone acetylation and gene transcription.
- Blocking glycolysis or pyruvate dehydrogenase (PDH) significantly reduces inflammatory gene expression, suggesting potential metabolic-targeted therapies.
- The inflammatory environment in JIA synovial fluid itself reprograms healthy T cells, reinforcing this glycolysis-acetylation link.
Why Does This Matter?
These findings provide support for targeting metabolism to reshape the epigenome of inflammatory T cells and help modulate immune responses in JIA and beyond.
Many thanks to all our essential collaborators, particularly ReumaNederland, for supporting this work.
Read the full study here
Paper: New Insights into Tumor-Immune Interactions
Our latest study reveals how colorectal cancer (CRC) tumors can directly shape the immune microenvironment by inducing a unique population of regulatory T (Treg) cells. Using a novel 3D organoid-T cell co-culture system, Sonia Aristin found that CRC tumor-derived organoids promote CD4+ T cell differentiation into a distinct, highly immunosuppressive Treg subset—without direct cell contact. These organoid-induced Tregs (TO-iTregs) have a unique transcriptional profile resembling tumor-infiltrating Tregs in CRC patients. Furthermore, high expression of TO-iTreg signature genes correlates with worse clinical outcomes in CRC. This model provides a new platform to explore immune regulation and develop strategies to disrupt tumor-induced immunosuppression.
Goodbye Enric!
After a decade in the Coffer Lab. senior scientist Enric Mocholi is heading back home to Valencia. Several generations of Coffers (2006-2024) joined to say goodbye. Enric has played an important role in the lab working on projects related to autophagy, metabolism and epigenetics, and co-supervising PhD students. We wish him success in setting up his own lab in Spain, and look forward to continued collaboration!
PhD survivor! Congratulations to Dr. Alessandro Cutilli
On October 17th, Alessnadro defended his PhD thesis titled: CD4+ and CD8+ behaviour in the landscape of intestinal damage: Prepare for trouble and make it double. Alessandro’s work investigated how CD4+ and CD8+ T lymphocytes behave during intestinal epithelial damage. Using co-cultures of human intestinal organoids and T cells, he examined chemotherapy's affect on intestinal cells and how this subsequently impacts T cell behaviour. Galectin-9 (Gal-9) was identified as a mediator that, when neutralized, reduces T cell proliferation and IFNγ production. Additionally he explored the effects of IFNγ-induced intestinal damage which was found to trigger the release of the chemokine CXCL11 promoting T cell migration. Finally Alessandro investigated T cell transcriptional repogramming in response to intestinal damage. These findings provide support for pre-clinical and prospective clinical investigations aimed at manipulating Gal-9 and CXCL11 to regulate T cell responses in the intestine.
You can learn more about Alessandro’s work if you click on the link here
Goodbye Cindy!
After 11 years in the Coffer Lab, Cindy Fredericks is leaving us to join Niels Eijkelkamp’s and Onno Krannenburg’s Labs. Cindy has played an essential role in the work of numerous PhD students and postdocs in the lab and she will be sorely missed. We wish her all the best with the new challenges!
Paper: How does interferon-mediated intestinal damage drive T cell recruitment?
Cytokines like interferon-gamma are key players in decisions driving inflammation and regeneration. Using a 3D co-culture model based on human intestinal organoids, PhD students Alessandro Cutilli and Suze Jansen discovered that interferon-gamma can reprogram the gut lining, leading it to express a set of pro-inflammatory genes. Specifically, they found an upregulation of chemokines CXCL9, CXCL10, and CXCL11—molecules that are key to recruiting immune cells. Their findings also showed that this reprogramming enhances T-cell migration, largely driven by CXCL11. These insights could open new therapeutic avenues: targeting CXCL11 might help prevent T-cells from trafficking to the inflamed intestine, potentially offering relief for conditions like inflammatory bowel disease (IBD). Check out the full study at:
https://pubmed.ncbi.nlm.nih.gov/39302156/