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2 Postdoctoral researcher positions

The Maurice group, based at the Center for Molecular Medicine at the University Medical Center Utrecht, and member of the national Oncode Institute, The Netherlands, has open positions for 2 postdoctoral researchers. We are looking for highly motivated and talented candidates that can join our team in the summer of 2021. The recruited postdocs will work closely with other members of our team to address molecular aspects of renewal and regeneration in intestinal and pancreas (cancer) tissues, using state-of-the-art technologies including genome editing, genomics, proteomics, (single cell) transcriptomics and imaging with organoid-based disease models.

Our research

The overall aim of our research group is to gain a fundamental understanding of the dual nature of signals that guide homeostatic tissue renewal and cancer cell growth. In healthy tissue renewal, a handful of signaling pathways supports the maintenance of small populations of adult stem cells. Deregulation of these pathways due to mutations is strongly linked to cancer development. Our main focus is to investigate how patient-derived mutations alter protein activity to promote the initiation and progression of cancer growth. With these insights we aim to uncover patient-specific disease mechanisms and develop improved cancer-targeting strategies. For more information, please visit: https://madelonmauricelab.nl/

Job descriptions

Postdoctoral position 1: Wnt niches in cancer

A 1.5-year postdoc position, funded by Oncode, is available in our laboratory to investigate the role of Wnt niches in colorectal and pancreatic cancer subsets that display Wnt-dependent growth. In this project, we aim to identify and characterize populations of Wnt-producing niche-like cells and investigate the transcriptional programs and cell lineages that are induced by autocrine Wnt signaling within these cancer subsets. The approaches and methodologies involve organoid culture, genome editing, biochemistry, reporter assays, advanced (live) imaging, (single cell) RNAseq analysis, and mass spectrometry.

Postdoctoral position 2: LKB1 mutations and cancer predisposition

A 3-year postdoc position, funded by the Dutch Cancer Society, is available in our laboratory to investigate how hereditary LKB1 mutations generate a state of gastrointestinal cancer predisposition in patients suffering from Peutz-Jeghers syndrome (PJS). In collaboration with Amsterdam UMC, we will generate a living biobank of intestinal PJS organoids to investigate how LKB1 loss affects intestinal cellular organization and function. Furthermore, in collaboration with Prof. Edwin Cuppen, we will investigate how LKB1 loss influences the mutational landscape to drive tumor growth. The approaches and methodologies involve organoid culture, genome editing, advanced (live) imaging, (single cell) RNA and DNA sequencing, in vitro and in vivo modeling of tumor growth, and mass spectrometry.

Your qualifications and expertise

For both positions, we are looking for highly motivated, ambitious and creative candidates, with the following competencies and experience:

  • You have a PhD in molecular or cell biology, preferentially with a strong background in tissue renewal and cancer biology
  • Experience in the computational analysis of bulk and/or single-cell RNA sequencing data will be regarded as a strong advantage
  • You have an ability to independently envision, plan and execute a research project
  • You have excellent technical skills; preferably, you have experience with culturing cells/organoids and applying CRISPR-based technologies
  • You have excellent communication skills in English, both verbally and written
  • You are committed to work in a team

Work environment

You will be based at the at the Center for Molecular Medicine (CMM) of the University Medical Center Utrecht (UMCU), in Utrecht, The Netherlands (https://www.umcutrecht.nl/en/research/center/center-for-molecular-medicine). The Maurice group is also affiliated with the national Oncode institute for cancer research https://www.oncode.nl/. We offer creative and stimulating working conditions in a dynamic, international and collaborative research environment. Our institute harbors modern laboratories and offers direct access to a number of advanced core facilities, including genome sequencing, single cell technologies, and proteomics. We have weekly meetings for data sharing, journal clubs, seminars with invited international speakers as well as opportunities to join the postdoctoral network Utrecht (PNU) that offers tailored training programs and career events https://www.uu.nl/en/education/graduate-school-of-life-sciences/postdocs/postdoc-network-utrecht).

Terms of employment

Your salary will be based on a full-time and fixed-term appointment of 36 hours, and the terms of employment are in accordance with the Collective Labour Agreement for University Medical Centers (CAO UMC). Both positions may be filled as per July 1, 2021.

Application process

Please send a single PDF document containing a cover letter with your motivation, a summary of previous research activities, curriculum vitae including publication list, as well as contact details of 2 references to m.m.maurice@umcutrecht.nl, before June 15, 2021.

Information

Information regarding the lab and institute can be obtained at: https://madelonmauricelab.nl/, and https://www.umcutrecht.nl/en/research/center/center-for-molecular-medicine

For more information about this position, please contact Dr. Ingrid Jordens (i.jordens@umcutrecht.nl) or Prof. Madelon Maurice (m.m.maurice@umcutrecht.nl)

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Welcome Susanna

In February 2021 Susanna Plugge joined our lab as a PhD student. Susanna will work on the role of LKB1 mutations in colorectal cancer development of patients with Peutz Jegher Syndrome.

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Review on WNT tumour suppressor mutations in cancer

Our lab published a new review in Nature Reviews Cancer with the title “Mutations and mechanims of WNT pathway tumour suppressors in cancer”. We discuss recent advances in the understanding of how different mutational subsets in WNT pathway tumour suppressors in human cancer link to distinct cancer types, clinical outcomes as well as treatment strategies

The publication can be found here.

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Goodbye Alessa

In October 2020 we said goodbye to Alessandra Merenda, who finished her post-doc in our lab. Alessandra started her new adventure as a scientist at HUB organoids. She received three gifts from the lab: a giant chocolate organoid cake, a jar of fortune candies (instead of fortune cookies), and a big photo book with personal messages from the group members. We will miss you, Alessa! And we hope to organize a proper goodbye dinner or borrel when this is allowed again.

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KWF grant for investigation of LKB1 mutations

In september 2020, the KWF (Royal Dutch Cancer Foundation) allocated 660.000 euros in funding for our lab to investigate how hereditary mutations in the LKB1 gene promote alterations in epithelial organization to generate a state of cancer predisposition in patients suffering from Peutz-Jeghers syndrome. We will perform this research in collaboration with our neighbors of the group of professor Edwin Cuppen.

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A novel class of oncogenic RNF43 mutations

Our publication describing how RNF43 mutations mediate a tumor suppressor-to-oncogene switch in cancer is now online at the EMBO Journal. The full article can be found here.

A video summary of our findings can be found here.

Tumor suppressor genes play an essential role in preventing uncontrolled cell division and thereby prevent cancer initiation; similar to the brake in a car. According to the dogma, cancer mutations in such a tumor suppressor genes cause loss-of-function of the gene resulting in a dysfunctional brake leading to uncontrolled growth and cancer formation. However, mutations in genes often do not result in a complete loss of the encoded protein, but rather create a shorter truncated version of the protein. The role of which is often unclear.

We previously discovered that the tumor-suppressor RNF43 controls the growth of intestinal stem cells by performing a negative feedback role in the Wnt-signaling pathway. Mutations in RNF43 are found in a variety of cancer types, including colorectal, gastric, endometrial, and pancreatic cancer. Mutations that result in loss of RNF43 function, make cancer cells hypersensitive for inhibitors of the growth signal Wnt.

However, we discovered a completely new class of RNF43 mutations that result in a shorter truncated protein. Instead of loss-of-brake function, these mutations endow RNF43 with a novel oncogenic role. Oncogenic RNF43 mutations can activate the Wnt signaling pathway in a ligand-independent manner, similar to pressing the accelerator pedal in a car. We introduced these oncogenic RNF43 mutations in human colon organoids and found that these colon organoids became insensitive to Wnt inhibitors.

Our study, therefore, stresses the importance of understanding the oncogenic mechanisms of mutations that are found in cancer patients. This is important for improved patient stratification for applications of precision medicine

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Paper on R-spondin signaling

In collaboration with the labs of Raj Rohatgi and Andres Lebensohn, we investigated the mechanism of LGR independent Wnt signaling potentiation by R-spondin. The results of this study have now been published in Elife: “R-spondins engage heparan sulfate proteoglycans to potentiate WNT signaling.” Check out the publication here.

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Publication on smFISH in organoids

In August 2019, our group published a new paper in Open Biology on single molecule FISH in organoids. Read this new publication here.

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Paper on VHHs targeting LRP5/6

In January 2019, our group published on VHHs targeting LRP5/6 in Nature Communications. Check this new publication here.

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Paper on TMEM59

In April 2018, our new paper on the role of TMEM59 in the Wnt signaling pathway was published. Check this new publication here.