Vercoulen Lab at UMC Utrecht
Unraveling the immune landscape
Spatial omics
Research
Immune dysregulation contributes to diseases such as cancer, chronic inflammation, and immune deficiency. The Vercoulen group develops spatial omics methods to analyze tissues and understand the inflammatory mechanisms that underly these diseases, and response to therapies .
Immune dysregulation and resulting disease can be facilitated by many factors in the tissue. The Vercoulen group aims to unravel the different cell types in the tissue microenvironment, and the crosstalk between cells that contributes to disease and therapy response.
To understand such complex processes, we develop and implement novel and innovative technology: mass cytometry (CyTOF). Mass cytometry allows analysis of single cells, and tissue sections in great detail, to identify cell types, behavior, and their location. We have recently developed a spatial method to analyze single cells in images generated with mass cytometry ‘MATISSE’. We perform spatial omics analysis of proteins, post-translational modifications, and RNA. We highly value our collaborations with fundamental, translational, and clinical colleagues, and strive to develop both innovative tools, generate and share knowledge, drive the field of spatial biology, and impact patient care.
Chronic inflammation and cancer
To study how chronic inflammation contributes to cancer initiation, we are studying a unique cohort of patients with severe inflammatory bowel disease, who are at high risk of developing colorectal cancer. To identify the underlying mechanisms, we apply spatial omics, which allows us to identify relevant cell types and signaling pathways, that localize in and around early cancerous tissue, that are further investigated and targeted in model systems, such as in vitro organoid culture systems. Our long-term aim here is to identify risk factors for cancer development and progress, and eventually molecular targets for safe preventive treatment.
Immune therapy in cancer
Different cancer immune therapy strategies have demonstrated their potency in the clinic, and T cell activation plays a major role in response. We are investigating mechanisms of action of cancer immune therapies, response and toxicity, for checkpoint inhibition therapy, and a novel IgA-based therapy. We study these processes in patient tissue biopsies, and in in vitro culture assays to assess mechanisms of action.
Signal transduction errors
Patients with inborn errors of immunity have defects in their immune system, and suffer from recurrent infections. Counterintuitively, these patients can also suffer from severe autoimmunity with high morbidity. Treating autoimmunity is difficult in these patients, since immune suppression may increase risk of infection. Therefore, we aim to unravel the underlying mechanisms of the disease, by modeling signal transduction upon in vitro receptor stimulation in T cells, and visualizing the inflammatory processes in the tissue affected by autoimmunity.
Tissue heterogeneity: Segmentation and Spatial Analysis
Spatial tissue architectural information is generally ignored by downstream single-cell data analyses. We aim to develop spatial analysis tool for extracting quantitative and comprehensible information on the complex spatial relationships between different cell types and their microenvironments and their organizational features in complex tissues.
Latest updates
Publications
Krijgsman D*, Schubert S*, Kraaier LJ, Lu Y, van Avondt K, Verdonschot MEL, Leusen JHW, van den Heuvel MC, de Kleine RH, de Meijer V, Kraal KCJ, de Krijger RR, Zsiros J, Peng WC**, Vercoulen Y**. High-plex imaging of hepatoblastoma and adjacent liver in pediatric patients reveals a predominant myeloid infiltrate expressing immune-checkpoints Cancer Immunology, Immunotherapy 2025, DOI: 10.1007/s00262-025-04164-3 van Dam S*, Krijgsman D*, Kuçukkose E, Verdonschot MEL, Amini M, Blokx WAM, van Eijs MJM,Verheijden RJ, Kranenburg O,Suijkerbuijk KP,Leusen JH, Vercoulen Y. Anti-PD-1 treatment response is associated with the influx of circulating myeloid and T-cell subsets into the metastatic melanoma tumor microenvironment British Journal of Cancer 2025, DOI: 10.1038/s41416-025-03137-8Floor E*, Su J*, Chatterjee M, Kuipers ES, Ijssennagger N, Heidari F, Giordano L, Wubbolts RW, Mihaila SM, Stapels DAC, Vercoulen Y**, Strijbis K**. Development of a Caco-2-based intestinal mucosal model to study intestinal barrier properties and bacteria-mucus interactions Gut Microbes, 2025. DOI: 10.1080/19490976.2024.2434685Baars MJD*, Floor E*, Sinha N,*Ter LInde JJM, van Dam S, Amini M, Nijman IJ, ten Hove JR, Drylewicz J, Offerhaus GJA, Laclé MM, Oldenburg B, Vercoulen Y**. Multiplex spatial omics reveals changes in immune-epithelial crosstalk during inflammation and dysplasia development in chronic IBD patients iScience, 2024. DOI 10.1016/j.isci.2024.110550Kucukkose E*, Baars MJD*, Amini M, Schraa SJ, Floor E, Bol GM, Borel Rinkes IHM, Roodhart JML, Koopman M, Laoukili J, Kranenburg O**, Vercoulen Y**. Stromal localization of inactive CD8+ T cells in metastatic mismatch repair deficient colorectal cancer British Journal of Cancer, 2024. DOI 10.1038/s41416-023-02500-xvan Eijs M, ter Linde JJM, Baars MJD, Amini M, Lacle MM, Brand EC, Delemarre EM, Drylewicz J, Nierkens S, Verheijden RJ,Oldenburg B, Vercoulen Y, Suijkerbuijk KPM,and van Wijk F. Highly multiplexed spatial analysis identifies tissue-resident memory T cells as drivers of ulcerative and immune checkpoint inhibitor induced colitis iScience, 2023. DOI 10.1016/j.isci.2023.107891Krijgsman D**, Sinha N*, Baars MJD*, van Dam S, Amini M, Vercoulen Y**. MATISSE: An analysis protocol for combining imaging mass cytometry with fluorescence microscopy to generate single-cell data. STAR Protocols, 2022. DOI: 10.1016/j.xpro.2021.1010van Dam S, Baars MJD, Vercoulen Y**. Multiplex Tissue Imaging: Spatial Revelations in the Tumor Microenvironment. Cancers, 2022. DOI: 10.3390/cancers14133170 Baars MJD, Sinha N, Amini M, Pieterman-Bos A, van Dam S, Ganpat MMP, Laclé MM, Oldenburg B, Vercoulen Y**. MATISSE: a method for improved single cell segmentation in imaging mass cytometry. BMC Biology, 2021. DOI: 10.1186/s12915-021-01043-yIjssennagger N, van Rooijen K, Magnusdottir S, Ramos Pittol J, Willemsen E; de Zoete M, Baars MJD, Stege P, Colliva C, Pellicciari R, Vercoulen Y, Kuipers F, van Mil S. Liver-gut axis controls the colonic mucus barrier via hepatic FXR. JHEP reports, 2021. DOI: /10.1016/j.jhepr.2021.100344Baars M, Douma T, Simeonov DR, Myers DR, Banerjee S, Kulhanek K, Zwakenberg S, Baltissen MP, De Roock S,vanWijk F, Vermeulen M, Marson A,Roose JP,Vercoulen Y**. Dysregulated RasGRP1 expression through RUNX1 mediated transcription promotes autoimmunity. Eur J Immunol, 2021. DOI: 10.1002/eji.201948451Nguyen NTB, Gevers S, Kok RNU, Burgering LM, Neikes H, Akkerman N, Betjes MA, Ludikhuize MC, Gulersonmez C, Stigter ECA, Vercoulen Y, Drost J, Clevers H, Vermeulen M, van Zon JS, Tans SJ, Burgering BMT, Rodríguez Colman MJ Lactate controls cancer stemness and plasticity through epigenetic regulation. Cell Metabolism, 2025. DOI 10.1016/j.cmet.2025.01.002Group members
Yvonne Vercoulen
Principal Investigator — y.vercoulen@umcutrecht.nl
“I am fascinated by immune regulatory mechanisms, with a focus on T cells, from fundamental to clinical. I trained as a PhD, working on Tregs at Utrecht University, and as a postdoc in molecular T cell immunology at UCSF, USA. Now I am Associate Professor & group leader at Center for Molecular Medicine , and scientific director of UCyTOF, and alumnus of Utrecht Young Academy.”
Mojtaba Amini
MSc – technician — m.amini@umcutrecht.nl
“I joined the group of Yvonne Vercoulen in 2017 and I am involved in several research projects in the group. I am manager of the UCyTOF Facility.”
Evelien Floor
PhD Candidate
“ I will study the role of JAK-STAT signaling and JAK inhibitors on tissue cells in chornic inflammation in the gut of patients with inflammatory bowel disease., using spatial proteomics and transcriptomics.”
Iria Lopez Estrada
PhD Candidate
“I started my PhD at the Leusen group (CTI) and Vercoulen lab (CMM). My research will focus on overcoming immunotherapy resistance in colorectal cancer by studying how myeloid immune cells limit treatment effectiveness.”
Aleksandra Reitupe
Master’s Student
“I am a master’s student in Cancer, Stem Cells and Developmental Biology, and I am doing a 9 month-long research project under the supervision of Evelien Floor. I will investigate the effect of various JAK inhibitors on epithelial-immune interactions, using co-culture systems of gut epithelial cells and immune cells.."
Faranak Heidari
PhD Candidate
“As part of the TOPGUT MSCA-DN project, I'll be undertaking my PhD at Utrecht University with Dr. Mihaila & Masereeuw and the Vercoulen lab. I will focus on developing a perfusable chip that replicates both the physiological functions and topographical features of the intestinal lumen, featuring crypt-villi-like patterned hydrogels seeded with intestinal PDOs. I will investigate the role of the stroma in tissue maturation and barrier function. Additionally, I'll assess the absorption and biotransformation of various molecules (e.g., bacterial, diet-derived, and drug molecules) from the gut.”
Kristof van Avondt
Assistant Professor—Spatial Omics Accelerator
“I am coordinating the Spatial Omics Accelerator at the UMCU”
Former members
Valerija Ivsiç
Master Infection and Immunity UU
Current: PhD candidate @Radboud U
Rhodé van der Kooij
Master Molecular and Cellular Life Sciences UU
Matthijs Baars
PhD candidate
Current: Scientist @Hubrecht Institute
Danielle Krijgsman
Postdoc
Current: Assistant Prof. @UMC Utrecht
Ian Molendijk
Master Drug Discovery & Innovation UU
Neeraj SInha
Postdoc, in Memoriam
Dorotea Neuberg
Master Science & Business UU
Current: Business Analyst @ Kearney
Meggy Verdonschot
Technician
Current: Technician @VUMC
Iris Langerak
Master Drug Discovery & Innovation UU
Current: CRA @ Julius Clinical
Annelies Pieterman-Bos
MSc Mol. & Cellular Life Sciences UU
Current: PhD candidate @UMCU
Pascalle Hemelop
BSc student & Technician
Current: Research associate @ Genmab
Maroussia Ganpat
Master Cancer Stem cells and Developmental Biology UU
Current: PhD @ Pr. Maxima Center
Sofia Frigerio
Visiting PhD candiate EU-Horizon project
Aleksandra Makowiezska
Visiting Postdoc
Current: Postdoc @ErasmusMC
Thera Douma
Master Biology of Disease UU
Current : Project leader @ Maag Lever Darm Stichting (gastrointestinal disease foundation)
Stephanie van Dam
PhD candidate
Current: MD at Flevoziekenhuis Almere
Sterre van Wierst
Master Cancer Stem Cells & Dev
Current: PhD @Wagening University
Thijs Demmers
Master Biology of Disease
Positions
If you are interested to join the lab, send an e-mail.
Funding
We are grateful to our funders:
Sacha Swarttouw-Hijmans Stichting. TKI-Health Holland Life Sciences Gastrostrart award (NVGE) KWF Kankerbestrijding
NWO-gravitation program CGC.nl
Strategic Program Cancer-UMCU
WKZ onderzoeksfonds AlfaSigma ISR Center for Unusual Collaborations (CUCo)
EU-Horizon
Contact
Twitter: @VercoulenYvonne
GitHub: VercoulenLab
UCyTOF.nl