Paper alert: Metabolism Meets Epigenetics in T Cell Function

We’re excited to share a new review from our lab that dives into a fascinating and rapidly evolving intersection of immunology, metabolism, and epigenetics.

In this review, we explore how subcellular pools of acetyl-CoA, a key metabolic intermediate, help shape the functional fate of T cells. Far beyond its classical role in energy production, acetyl-CoA acts as a molecular bridge between metabolic pathways and chromatin remodeling. By generating compartment-specific acetyl-CoA (in the mitochondria, cytosol, and nucleus), T cells adapt to changing environments and maintain flexibility in activation, differentiation, and memory formation.

The review highlights emerging mechanisms by which enzymes like ACLY, PDHc, and ACSS2 translocate to the nucleus and fine-tune gene expression through histone acetylation. These findings not only enhance our understanding of T cell biology but also point to potential metabolic-epigenetic targets in autoimmune diseases, infections, and cancer.

🔗 Read the full article here

We're hiring! Postdoctoral position in developmental signaling and nuclear metabolism

We are seeking an ambitious and talented postdoctoral scientist to join an exciting new ZonMw-funded project that aims to unravel how intracellular metabolism and transcription co-regulate embryonic development. This multidisciplinary research project brings together the complementary expertise of three Dutch institutes: the Coffer Lab (CMM, UMC Utrecht), the Sonnen Lab (Hubrecht Institute), and the Bauer Lab (TU Delft), offering a unique opportunity to work at the interface of developmental biology, biochemistry, and systems modeling.

Project Overview

Titled “Signal Symbiosis: Exploring the Co-Regulation of Metabolism and Transcription in Embryonic Cell Fate”, this project investigates how nuclear metabolic enzymes influence transcriptional reprogramming during mammalian somitogenesis. The research focuses on metabolic signaling pathways (glycolysis and acetyl-CoA generation), their nuclear partitioning, and how they interact with dynamic developmental signaling circuits such as Wnt and Notch. 

Using cutting-edge approaches—ranging from live cell imaging and metabolic biosensors, to proximity labeling and epigenomic profiling—the successful candidate will help uncover how nuclear metabolic events directly control gene expression and cell fate decisions in embryonic tissues and stem cell-derived organoid models.

The Position

The postdoctoral scientist will be based in the Coffer Lab at UMC Utrecht, a group with expertise in transcriptional regulation, metabolic control, and chromatin remodeling. You will collaborate closely with the Sonnen Lab, a leader in live imaging and microfluidic modeling of embryonic development, and the Bauer Lab, which brings quantitative systems biology and computational modeling expertise.

The successful candidate will take the lead in developing and applying novel biochemical tools to dissect nuclear metabolic complexes and their impact on chromatin state and transcriptional outcomes in developmental models.

Required Skills & Expertise

We are looking for a motivated and independent researcher with:

• A PhD in molecular biology, biochemistry, developmental biology, or a related field;

• Demonstrated experience with chromatin biology, transcriptional regulation, or metabolism;

• Strong molecular and cellular technical skills

• Experience with stem cell differentiation or 3D organoid models is an asset;

• Excellent communication skills and a collaborative mindset, ideally with experience in multidisciplinary projects.

What We Offer

• A dynamic, collegial environment at the Center for Molecular Medicine;

• Access to state-of-the-art technologies and expertise across three partner institutes;

• Mentorship, career development support, and the opportunity to co-supervise junior researchers;

• A full-time, fixed-term appointment with competitive salary and benefits, in accordance with Dutch academic standards.

Interested?

For more information or to apply, please contact Prof. Paul Coffer (pcoffer@umcutrecht.nl) with your CV, a cover letter outlining your research interests and connection with the project goals. Review of applications will begin immediately and continue until the position is filled.

PhD survivor! Congratulations to Dr. Sonia Aristin

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 alert: 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 alert: 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.

Read the full paper here

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