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Molecular Pathology: Jacco van Rheenen

Van Rheenen, Jacco

Jacco van Rheenen, Ph.D professorGroupleader

About Jacco van Rheenen

The van Rheenen group studies the identity, behavior, and fate of cells that drive tumor initiation, progression, metastasis and the development of therapy resistance. These populations of cells are difficult to study since they are rare, and their behavior (e.g. migration) and traits (e.g. stemness) change over time. To be able to study these dangerous cells, we have developed microscopy techniques to visualize individual cells in real-time in living animals, referred to as intravital microscopy. For example, we developed small imaging windows that can be surgically implanted in mice giving visual access to tissues with cellular precision for several weeks. Using intravital imaging, the van Rheenen lab revealed multiple important factors within the single cell heterogeneity that are crucial in the processes of tissue homeostasis, tumor initiation and tumor progression.

Our research focuses on four areas are (1) The cellular mechanisms of tissue development and homeostasis, tumor initiation, and tumor progression; (2) The cellular mechanisms of migration and metastasis of cancer; (3) The role of microvesicles in tumor heterogeneity and tumor progression; (4) The molecular and cellular mechanisms of chemotherapy resistance and side effects.

High resolution intravital microscopy:

Our group develops and utilizes state-of-the-art imaging techniques to visualize the adaptive properties of the few dangerous cancer cells (e.g. stem and/or migratory cells) within the large population of non-metastasizing and differentiated cancer cells. We combine the latest genetic tumor models with intravital imaging (the visualization of single cells in living mice). For this, we have developed techniques to trace individual tumor cells within the primary tumor and at distant organs in a living mouse for several weeks at subcellular resolution.

 Final conclusions:

The unique intravital imaging techniques developed in our lab enabled us to gain detailed information on the cellular behavior at single-cell level during both tissue homeostasis and tumor initiation and progression. This unique way of studying these processes has led to major breakthroughs in the fundamental understanding of cancer.

More research details

 

View more (layman's) explanatory movies

 

Co-workers

Azkanaz, Maria

Maria Azkanaz

PhD student

Experience

In September 2019, I joined the group of Jacco van Rheenen as a PhD student. My project focuses on studying the cellular and molecular mechanisms that underlie intestinal epithelial homeostasis and response to damage as well as initiation, progression and metastasis of colorectal cancer using intravital microscopy.

Before joining the NKI, I obtained a bachelor degree in Biology and Medical Laboratory Research at Saxion University of Applied Sciences in Enschede and a Pre-Master's and Master's degree in Biomedical Sciences at University of Groningen. During my Master's, I completed two internships in the field of hematology and oncology in the labs of Dr. Jan Jacob Schuringa at University Medical Centre Groningen and Dr. John Dick at Princess Margaret Cancer Centre in Toronto, Canada.

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Beerling, Evelyne

Evelyne Beerling

Technician / Research Associate

Experience

I joined the Van Rheenen team in 2010 as a PhD student, focusing on intravital imaging of different types of cancer to study tumor cell migration, the role of epithelial-to-mesenchymal transition (EMT) in tumor cell dissemination and the response of tumor cells to chemotherapy, all using in vivo models. While finishing up my PhD I started as a technician in Jacco's group in 2014. My job mainly consists of keeping the lab and our animal colony organized, assisting others with their projects and teaching internal as well as external people our imaging window techniques.

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Bornes, Laura

Laura Bornes

Ph.D. Student

Experience

I obtained my BSc and MSc in medical biology at the University Duisburg-Essen. During my internships at BayerTS,  the p53lab at A*STAR as well as in the Knauer Lab I got into contact with cancer research from different angels. I had the chance to have a closer look into assay development, and high-through put screens to find new targeting compounds but also into fundamental research.

In October 2015 I started my PhD in Jacco van Rheenen's group. My projects evolve around how mammary tumors metastasis. I'm looking into which role active migration plays in metastasis formation and whether there are targets in the metastatic cascade.

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Bruens, Lotte

Lotte Bruens

Ph.D. Student

Experience

After obtaining my Master degree in "Cancer, Stem Cells and Developmental Biology" at Utrecht Univeristy, I joined the group of Jacco van Rheenen in 2014 to start my PhD. I am also part of the Hugo Snippert group at the UMC Utrecht.

My projects mainly focus on homeostasis in the intestinal epithelium and how the epithelium copes with aberrations in this homeostasis. Using intravital microscopy I uncovered a process called crypt fusion, an almost exact reversal phenomenon of crypt fission, during which two crypts fuse into one daughter crypt. I am currently investigating which mechanisms underlie crypt fission and fusion. In addition, I am looking at the effect of calorie restriction on intestinal homeostasis.

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Chen-Zijlstra, Linda

Linda Chen-Zijlstra

Postdoctoral Fellow

Experience

I am the imaging expert and facility manager at the van Rheenen's lab. Before I joined NKI, I was working as an imaging specialist at SVI, I am familiar with the Huygens software and expertise on image processing. My other experience include: I was a research scientist at toBBB in the Leiden bioscience park. I was working on the mechanism of glutathione-conjugated liposome enhance drug delivery. I finished my PhD at RMIT University, Australia on vaccine development. Then I was working at Swinburne University and  studied the effect of radiofrequency radiation on the blood-brain barrier with different imaging techniques.  

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Damen, Maartje

Maartje Damen

Ph.D. Student

Experience

In March 2020, I joined the van Rheenen lab to start my PhD. My project mainly focuses on the role of the epithelial-mesenchymal transition in cancer metastases and therapy resistance.

Before joining the team, I obtained my master's degree in Biomedical Sciences (oncology track) at the University of Amsterdam. As part of this program I looked into the effects of hypoxia on radiation sensitivity in the lab of Dr. Rene Medema at the NKI. During my second internship, I characterized a novel probe in targeted photodynamic therapy in the group of Dr. Gang Zheng at the Princess Margaret Cancer Centre in Toronto.

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Hahn, Kerstin

Kerstin Hahn

Postdoctoral fellow

Experience

I'm working as a postdoc in the lab of Prof. J. van Rheenen. I'm investigating cell cycle-related effects of radiotherapy in BRCA1-deficient mammary tumors using intravital microscopy, financed by a grant of the Swiss National Science Foundation.

My previous research includes BRCA1 and 2 deficient breast- and ovarian cancer (mouse models, organoids) with focus on residual disease (Lab Prof. S. Rottenberg), neuropathology, neurodegeneration, neuroinfectiology and virus discovery (Lab Prof. W. Baumgärtner, Lab Prof. K. Schughart). Besides, I'm a ECVP board certified veterinary pathologist with specialization on comparative pathology and training in toxicologic pathology.

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Krotenberg Garcia, Ana

Ana Krotenberg Garcia

Ph.D. Student

Experience

I obtained my Bachelor in Biotechnology in Salamanca University and moved to The Netherlands to study the Master of Biology of Disease in Utrecht University. Once graduated, I worked as a technician in Christine Mummery's lab in the LUMC. Recently, I started my PhD in Jacco van Rheenen's group under the supervision of Saskia Suijkerbuijk, together we are working on a research line based on cell competition. 

My PhD project is focused on unraveling the cellular and molecular mechanisms involved in cell competition between CRC liver metastasis and healthy liver cells, with the potential prospective of using this knowledge in therapy.

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Lohuis, Jeroen

Jeroen Lohuis

Ph.D. Student

Experience

I have obtained my master's degree in biomedical sciences at Utrecht university in 2017. I performed my first masters internship in the lab of Jacco van Rheenen, where I now work as a research technician.

My research is aimed at getting a better understanding of the recurrence of cancer upon therapy, with a special focus on possible unintended side-effects of therapy that stimulate tumour recurrence. For this we use intravital imaging techniques to study tumour dynamics upon different treatments.

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Da Cruz Margarido, Andreia

Andreia Margarido

Ph.D. Student

Experience

I completed my Bachelor in Biology with a specialization in Genetics and Molecular Biology in Lisbon, Portugal. I continued my Master's degree in Developmental and Evolutionary Biology also in Lisbon and performed my internship abroad in Montpellier, France. Here I worked in the group of Dr. Pascal de Santa Barbara characterizing the development of lymphatic and enteric nervous system in the gut.

At the end of 2015, I joined the van Rheenen lab to work on brain metastasis and perform intravital microscopy.

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Messal, Hendrik

Hendrik Messal

Postdoctoral fellow

Experience

I am a postdoc in Jacco van Rheenen's team where I explore the mechanisms that drive tissue remodeling in regeneration and cancer. My technical approach includes intravital microscopy, whole organ imaging, genetic interference, single-cell omics and mathematical modeling.

Before joining the NKI, I did my PhD at the Francis Crick Institute in London in the lab of Axel Behrens where I developed a technique for 3D whole organ microscopy.  I employed this technology to quantitatively describe tumour progression in the pancreas and uncovered a fundamental principle by which the local tissue geometry instructs adult tissue morphogenesis and modulates neoplasia biology.

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Morgner, Jessica

Jessica Morgner

Postdoctoral fellow

Experience

During my PhD in the group of Sara Wickstroem at the Max-Planck Institute for Biology of Ageing in Cologne, Germany, I studied the role of key adhesion mediators in regulating cell fate downstream of
cell-matrix adhesions. In 2016 I joined Jacco Van Rheenens group at the Hubrecht Institute in Utrecht and was awarded an EMBO fellowship. After moving with the group to the NKI, I continued investigating the dynamics of cell-matrix interactions in cancer progression and metastasis formation by using
intravital imaging techniques.

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Scheele, Colinda

Colinda Scheele

Ph.D. Student

Experience

I am a PhD student in the lab of Jacco van Rheenen, and I started my project in June 2014. During my PhD I aim to understand how the healthy mammary gland develops and grows, and how these processes are perturbed during mammary tumor development. To do so, I am using lineage tracing in genetic mouse models, combined with intravital microscopy, single cell mRNA sequencing, and mathematical modelling. Before I started my PhD, I obtained a Master degree (Cancer, Stem Cells and Developmental Biology) and a Bachelor degree (Biomedical Sciences) at Utrecht University.

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Schelfhorst, Tim

Tim Schelfhorst

Technician

Experience

I obtained my bachelor degree in February 2015 from Saxion University of Applied Sciences in Enschede. After my final internship in the VUmc, I started working as a technician in the   oncoproteomics lab of Connie Jimenez.

Because of the nature of the group we had many collaborations and one of which was Sander Steenbeek, a PhD student from the group of Jacco.

In September 2018 I joined the Jacco van Rheenen group as a technician.  

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Suijkerbuijk, Saskia

Saskia Suijkerbuijk

Senior Scientist

Experience

I am interested in a process called cell competition and in particular how tumors use this mechanism. This interest was developed in the lab of Euginia Piddini (Gurdon Institute, Cambridge, UK), where I moved after I finished my PhD in the lab of Geert Kops (UMC Utrecht). My current focus is involvement of cell competition in colorectal cancer, both at the primary site and during metastasis. With a combination of organoid and mouse models I investigate how cell competition affects tumor growth and how we could target cell competition for treatment colorectal cancer.

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Vennin, Claire

Claire Vennin

Postdoctoral fellow

Experience

I completed my PhD studies at the Garvan Institute of
Medical Research (Sydney, Australia) under the supervision of Dr. Timpson,
where I studied how tissue stiffness within pancreatic tumors affects disease
progression and response to therapies. In 2018, I joined the Van Rheenen
laboratory and I obtained a HFSP fellowship. I am specifically interested in
how interactions between tumor cells and their environment influence cancer
development, and during my post-doc I will apply the microscopy techniques developed
by the van Rheenen lab to interrogate how crosstalk between dormant cancer
cells and neighbor cells affect the tumor immune response.

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Vizoso Patino, Miguel

Miguel Vizoso Patino

Postdoctoral fellow

Experience

In 2016, I completed my PhD in Biomedicine at Barcelona University. During my PhD I focused on the epigenetic regulation of metastatic driver genes in melanoma, colorectal and breast cancer. However, since these kind of analyses are performed at a fixed time points, information of the plasticity of individual cells is lost. Following my curiosity, I could join van Rheenen's group at the end of 2016 and got the postdoctoral EMBO long term fellowship in 2017 with the aim to visualized the dynamics of DNA methylation during tumor progression by using high resolution intravital microscopy.

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Uceda Castro, Rebeca

Rebeca Uceda Castro

Ph.D. student

Experience

After obtaining my Master's degree in "Biochemics, Molecular Biology and Biomedicine" at Universidad Complutense of Madrid, I joined the group of Jacco van Rheenen to start my PhD.

During my Master degree I was working with Chronic Lymphocytic Leukemia at Angeles Garcia Pardo's lab at the CIB-CSIC.

My project in Jacco van Rheenen group is focus on studying the intermediate filament network in glioma invasion using different techniques.

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Key publications View All Publications

  • Identity and dynamics of mammary stem cells during branching morphogenesis

    (2017) Nature. Feb 16;542(7641):313-317. doi: 10.1038/nature21046. Epub 2017 Jan 30.

    Scheele CL, Hannezo E, Muraro MJ, Zomer A, Langedijk NS, van Oudenaarden A, Simons BD, van Rheenen J.

    Link to PubMed
  • In Vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior

    (2015) Cell. May 21;161(5):1046-1057. doi: 10.1016/j.cell.2015.04.042.

    Zomer A, Maynard C, Verweij FJ, Kamermans A, Schäfer R, Beerling E, Schiffelers RM, de Wit E, Berenguer J, Ellenbroek SIJ, Wurdinger T, Pegtel DM, van Rheenen J.

    Link to PubMed
 
 

Recent publications View All Publications

  • Poor perfusion of the microvasculature in peritoneal metastases of ovarian cancer

    (2020) Clin Exp Metastasis. Feb 1. doi: 10.1007/s10585-020-10024-4.

    Kastelein AW, Vos LMC, van Baal JOAM, Koning JJ, Hira VVV, Nieuwland R, van Driel WJ, Uz Z, van Gulik TM, van Rheenen J, Ince C, Roovers JWR, van Noorden CJF, Lok CAR.

    Link to PubMed
  • Fsp1-Mediated Lineage Tracing Fails to Detect the Majority of Disseminating Cells Undergoing EMT

    (2019) Cell Rep. Nov 26;29(9):2565-2569.e3. doi: 10.1016/j.celrep.2019.10.107.

    Bornes L, van Scheppingen RH, Beerling E, Schelfhorst T, Ellenbroek SIJ, Seinstra D, van Rheenen J.

    Link to PubMed
 

Contact

  • Office manager

    Suzanne Romijn

  • E-mail

    s.romijn@nki.nl

  • Telephone Number

    +31 20 512 9168

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