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Vercoulen
Vercoulen

Vercoulen

Areas of expertise

Yvonne trained as a PhD student with Berent Prakken and Paul Coffer (UMC Utrecht). She studied regulatory T cells (Tregs) in health and inflammatory disease. Here, she developed her enthusiasm for translational research, and investigated Treg properties, from molecular mechanisms to in vivo functionality, in patients and mice. She established properties of Tregs that could be related to clinical outcome in patients with inflammatory disease.
To obtain a deeper understanding of how this is regulated on a molecular level, she joined Jeroen Roose’s lab at UCSF (San Francisco, USA) in November 2011 as a postdoctoral fellow. She was awarded a Marie Curie IOF Fellowship (2012) to study the Ras guanine nucleotide exchange factor RasGRP1, and how it regulates lymphocyte receptor signaling pathways. Yvonne gained expertise in molecular biology, biochemistry and mouse immunology, and is currently combining these skills with translational research in patients.
In October 2016, she was recruited to the Center of Molecular Medicine to initiate her independent research line. In particular, Yvonne aims to understand how inflammatory processes influence intracellular signaling pathways that contribute to cancer development.

Imaging Mass Cytometry analysis of complex tissue

Research program/Group

Cancer development and progress is a complicated process, facilitated by many factors in the tissue. The Vercoulen group aims to unravel:

  • the different cell types in the tumor and the microenvironment, and
  • the intracellular signaling pathways

that contribute to cancer development. We take a discovery approach analyzing key signaling proteins expressed in the different cell types in tumors and the microenvironment. In order to understand such complex tissues, we apply a novel and innovative technology: mass cytometry (CyTOF). Mass cytometry allows analysis of single cells, as well as tissue sections in great detail (30-50 parameters, Figure 1). This will provide us with highly relevant information on numbers of cell types present, as well as their location in the tissue, which signaling pathways are active, cell behavior (proliferation, cell death, production of soluble factors), and which receptors are expressed.

Chronic inflammation and cancer
For example, in a cohort of patients with inflammatory bowel disease, who are at high risk of developing colorectal cancer, we will apply this approach to identify the cell types and signals that contribute to the development of dysplasia and cancer.

Our discovery approach allows us to identify relevant cell types and signaling pathways, that are further investigated and targeted in model systems, such as in vitro organoid culture systems. Our long-term aim is to identify risk factors for cancer development and progress, and eventually molecular targets for treatment.

Molecular regulation of Ras signaling by RasGRP1
We aim to understand how exactly the RasGEF RasGRP1 (Figure 2) contributes to aberrant Ras signaling. Hereto, we are currently further exploring the molecular mechanisms that regulate RasGRP1 expression and activation.

Model displaying the mechanisms of RasGRP1 autoinhibition and activation.

In the news

Hundreds of thousands of people in Europe are affected by autoimmune disorders such as arthritis, lupus and inflammatory bowel disease, and rates are rising. But there are few effective long-term treatments, and little is known about the underlying triggers that cause T cells to attack healthy tissue. That’s where the EU-funded AUTOIMMUNITY RASGRP1 project comes in. “T cells are the ‘bad guys’ in autoimmunity,” says researcher Yvonne Vercoulen, project coordinator (UMC Utrecht, Netherlands). “So we wanted to know what happens inside a T cell when things go wrong and they turn on us.” Here you can read the whole interview with Yvonne Vercoulen,  entiteld "Getting to grips with autoimmunity". (published: 20 June 2018)

Group members

  • Yvonne Vercoulen - PI
  • Mojtaba Amini, MSc - technician
  • Matthijs Baars -  PhD student
  • Stephanie van Dam - PhD student
  • Iris Langerak - Master student

Key publications

  • Baars M, Douma T, Simeonov DR, Myers DR, Banerjee S, Kulhanek K, Zwakenberg S, Baltissen MP, De Roock S, van Wijk F, Vermeulen M, Marson A, Roose JP, Vercoulen Y. Dysregulated RasGRP1 expression promotes autoimmunity. BioRxiv June 6, 2019. https://doi.org/10.1101/656454
  • Vercoulen Y, Kondo Y, Iwig JS, Janssen A, White KA, Amini M, Barber DL, Kuriyan J, Roose JP. A histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1. Elife. 2017 Sep 27;6. pii: e29002. doi: 10.7554/eLife.29002. [Epub ahead of print] PMID:28952923.
  • Iwig JS, Vercoulen Y*, Das R*, Barros T, Limnander A, Che Y, Pelton JG, Wemmer DE, Roose JP, Kuriyan J. Structural analysis of autoinhibition in the Ras-specific exchange factor RasGRP1. Elife. 2013; 2:e00813. 
  • Vercoulen Y*, Guichelaar T*, Meerding J, Emmelot M, Pingen M, Storm G, Coffer PJ, Sawitzki B, Martens A, Mutis T, Prakken BJ. Application of cultured human regulatory T cells requires preclinical in vivo evaluation. Journal of Allergy and Clinical Immunology, 2012 Mar;129(3):852-855.e3.
  • de Kleer I*, Vercoulen Y*, Klein M, Meerding J, Albani S, van der Zee R, Sawitzki B, Hamann A, Kuis W, Prakken B. CD30 discriminates heat shock protein 60-induced CD4+FOXP3+ T cells with a regulatory phenotype. The Journal of Immunology. 2010 Aug 15;185(4):2071-9. 

Link to full list of publications

More contact information

Visiting address
Stratenum, room number 3.205
Universiteitsweg 100
3584 CG Utrecht
The Netherlands

Secretariat
Cristina Arpesella
m.c.arpesella@umcutrecht.nl
+31 88 75 68988