van Amerongen Lab - Developmental, Stem Cell & Cancer Biology

Review chapter out online

A new review, in which Saskia and Renée zoom in on the working mechanism of the WNT/CTNNB1 destruction complex, came out online today. It looks like the DOI has not been activated yet, but you can access the review (titled "Zooming in on the WNT/CTNNB1 Destruction Complex: Functional Mechanistic Details with Implications for Therapeutic Targeting") here:
https://link.springer.com/content/pdf/10.1007%2F164_2021_522.pdf

We are quite happy with how it turned out and are curious to hear what you think.

13 September, 2021

Goodbye students and welcome Anna!

Before the start of the academic year 2021-2022, we said goodbye to our students (Omayma and Uliana gave their talk before the summer break and handed in their reports, Melanie and Jenny presented their work today and are wrapping up the writing and Jobana will wrap up this month).



We celebrated the end of their pandemic, largely in silico internships with lunch at the Polder and two new group shots, including one in our new composition: Anna joined us today for her 9 month HLO internship.

Welcome Anna and happy trails to everyone who is moving on to the next steps!

1 September, 2021

New pre-print

Just before the summer break we published a new pre-print.

Titled "Hyperactive WNT/CTNNB1 signaling induces a competing cell proliferation and epidermal differentiation response in the mouse mammary epithelium", this study uses a 3D primary mouse mammary organoid culture system to study the immediate (early or direct) consequences of hyper activating the WNT/CTNNB1 response in the mammary gland.

As we know from cumulative work in the field and as also consistently supported by our own experiments, the mammary epithelium is quite sensitive to the absolute levels of WNT/CTNNB1 signaling. In this study we tweak apart the molecular and cellular responses of the mammary epithelium apart in response to low, medium and high levels of WNT/CTNNB1 signaling.

Now let us hope that this study finds a permanent peer-reviewed home (the first rejection landed on our desk when we returned from our summer holidays, so we are now digesting the reviewer comments).

Kudos to everyone in the lab who has contributed to this work over the past 8 (!) years, including former technician Amber Zeeman and former postdocs Larissa Mourao and Katrin Wiese, as well as multiple students who have worked on this project over the years during their MSc internships (Anika, Lieve, Isabel).

28 July, 2021

New publication: Paper accepted in eLife and out online

We are very excited to announce that after a long and strenuous, but altogether very positive and constructive review process, our study "Quantitative live-cell imaging and computational modelling shed new light on endogenous WNT/CTNNB1 signaling dynamics" by De Man et al. has been accepted for publication by eLife!

We are editing the proofs as we speak, but the paper is already out online and can be accessed here: https://elifesciences.org/articles/66440.

This tour de force was led by first author Saskia de Man, who is currently on a research visit in the United States. This means that we had to have transatlantic cake moments to celebrate, but that didn’t diminish our joy (and relief). Tanne van der Wal also contributed to the final version of this work, where we combine quantitative live cell imaging and computational biology to determine the absolute amounts and complex states of endogenous wildtype CTNNB1 and an oncogenic S45F mutant. This was only possible thanks to a collaboration with our colleagues Gooitzen Zwanenburg and Mark Hink. Kudos to Saskia for integrating all of our expertise and staying on top of it all.

We are also very excited that our artist in residence, Rosa Schogt, composed a poem inspired by this work for the occasion, which we are officially launching today to accompany the paper (in Dutch, below):



A Twitter thread with more details can be found here.

For the WNT aficionados: One thing our data reveals is that, contrary to our expectations, the multivalent destruction complex might only have limited occupancy (i.e. rapid turnover and release) of CTNNB1, with higher occupancy only being detectable for the S45F mutant form of CTNNB1.

We draw an analogy between the destruction complex and an old fashioned waterwheel: "Even if the multivalent destruction complex offers multiple CTNNB1 binding sites, occupancy at any one time might be low, due to the continuous and high turnover of CTNNB1. In this respect, the CTNNB1 bindings sites in the destruction complex could be envisioned to act similar to the wooden vanes in the paddle wheel of an old-fashioned watermill: like the water in the analogous example, CTNNB1 would be continuously scooped up (for phosphorylation) and dropped off (for degradation)."

We were afraid that the figure we drew to illustrate this concept would not be deemed quite scientific enough, so we only included it in one of our rebuttals (thank you, Reviewer 1, for liking this analogy). So here it is for the more visually inclined:

9 July, 2021

The very first Wntlab PhD defense: Nika becomes dr. Heijmans

On Wednesday morning Nika successfully defended her PhD thesis, thereby becoming the first dr. to come out of the lab. Congratulations Nika on such a beautiful thesis and a job well done!

Luckily, the COVID-19 measures were alleviated just in time for a hybrid defense: while seating was limited, the ceremony did take place in the beautiful old Agnietenkapel in the center of Amsterdam with a beadle and two paranymphs. Two external committee members joined us from Utrecht via livestream, while the president of the committee and the three other committee members along with the promotor and co-promotor were physically present. And, most importantly, some close family, friends and (former) colleagues could attend. After such a long time of online only we are counting our blessings that we got to enjoy something that came really close to a good old fashioned PhD defense!

7 July, 2021

Lab BBQ

Tanne hosted a lab BBQ to celebrate summer and the (upcoming) end of the BSc and MSc internships. This was the first time we were all together, timed with scientific precision in the week in which COVID-19 levels were at their lowest (that was fun while it lasted).

The students outnumbered other lab members this year, requiring flexibility from all involved. All things considered, we think we have been able to offer decent internship experiences under the circumstances (looking at you, pandemic).


Roasting marshmallows brings out the best (and inner child) in everyone!

7 July, 2021

Coffee break and impromptu lab picture

We had our first coffee break with the entire lab in the new constellation. We can only imagine what exciting development will still occur on this patch of land that makes it look like we live somewhere out in the desert or on a building site (we have high hopes for a Friends style fountain, but it looks like it might just be plain old grass). In either case, the wall did allow us to soak in the sun and pose for a socially distanced lab picture. Let’s hope this is the last 1.5 meters one!


Thank you Eike for taking the picture!

2 June, 2021

Marleen joins the lab as a new PhD student

Today, Marleen started as a PhD student in the lab. She will work on dissecting how tissue specific WNT signalling is initiated and interpreted. Hopefully in the next few years, we will solve some longstanding questions together.

Welcome Marleen!

1 June, 2021

New publication: Behind the scenes of the human breast cell atlas project

Renee wrote a perspective for a special edition of the Journal of Mammary Gland Biology and Neoplasia that focuses on single-cell techniques. She also served as guest editor for this special issue, together with Zuzana Koledova (Czech republic) and Edith Kordon (Argentina).




The special issue is still being finalized, but the paper came out today and is available as an open access article here. Thanks to Kai Kessenbrock, Whalid Khaled, Devon Lawson, Harikrishna Nakshatri and Nicholas Navin, who shared their first-hand experiences to get this behind the scenes look.

29 April, 2021

Publication from a collaboration

Good things come to those who wait and patience is a virtue. These words definitely apply to this study that was just accepted for publication in Development.

Titled "MEIS-WNT5A axis regulates development of 4th ventricle choroid plexus", this paper dissects in great detail how a particular part of the fluid filled spaces in our brain (the so called ventricles) develops. Within these ventricles, a tissue called the choroid plexus is responsible for producing the fluid that fills these spaces. This so called cerebrospinal fluid extends all the way down to our spine (and now you know where Spinal Tap got its name).

Renee is a co-author on this study, which was led by Karol Kaiser and Vita Bryja in a collaboration with groups in Boston and Stockholm. As for the tiny little part that we contributed: somewhere between 2011 and 2014 Renee performed timed matings with the Wnt5a transgenic mouse model while being on the tenure track and setting up the lab. Over the years, we have watched this work progress from posters to PhD theses to a pre-print and now a formally peer reviewed and accepted paper.

We are glad to work in a field where we have colleagues that still remember such contributions almost a decade later and we hope to pay it forward. At the same time, this story underscores how much effort and how many years of work can go into getting a story published these days, but that is something for another post.

update 31 May 2021: now officially published.
Development (2021) 148 (10): dev192054. https://doi.org/10.1242/dev.192054

26 April, 2021

ENBDC Weggis workshop

No fresh mountain air or foggy morning views across the lake, unfortunately, as the ENBDC Methods Workshop was held via zoom this year. On the bright side, this meant we could afford to take all of our MSc students to an international conference! Hopefully the organizers do not mind that our BSc students also dropped by for the Friday morning session on development.

To add a bit of atmosphere instead of turning this into just another zoom event, we watched the talks and had lunch together at the appropriate social distance.

22 April, 2021

Welcome Demi and Tiba

For the first time in history, we will have two BSc students joining the lab while performing their actual lab work more remotely in one of the teaching buildings.
Thanks to the creative improvisation skills of everyone involved in our Biomedical Sciences program, some of the BSc internships can continue in this way.

Demi an Tiba picked our project and will be running back and forth between the teaching lab and Thijs’ office for specific help and advice for when the cloning gets tough. They will also join our lab meetings, so they will hopefully still feel like part of the lab despite this long distance solution.

1 April, 2021

Saskia visits the NIH

After a long period of insecurity as to whether travel to the United States would actually be possible mid-pandemic, a small miracle happened and Saskia left for a research visit to the NIH, where she will be working in the lab of Andres Lebensohn for the last part of her PhD.

We already adjusted the time of our weekly lab meetings so Saskia can still join from across the pond as she sets up this exciting research collaboration.

This visit was made possible by a grant from the Nijbakker Morra foundation and a Fulbright Scholarship.

19 March, 2021

Welcome Uliana

Uliana is the last MSc student to join the lab for this academic year. She will join Jenny, Jobana and Omayma in using multiple online tools to generate new hypotheses for follow up research.

1 March, 2021

First seminar since the start of the pandemic

Renée gave her first talk since November 2019 (not counting teaching and outreach activities).

After still teaching a class on mouse models to the first year BSc students biomedical sciences on Friday afternoon, the wonders of the internet allowed her to present unpublished work from the lab at East Carolina University in the United States on Friday evening.

The seminar was hosted by Dr. Maranke Koster, and while it would have been nicer to visit in person and interact with a live audience, it was good to virtually visit an old friend and present a new story!

19 February, 2021

Welcome students

We did our best to create as many internship positions as we possible could to minimize the impact of the pandemic on the training of our MSc students.

Four out of five students started today. Melanie will be working under the supervision of Tanne to figure out how CTNNB1 balances cell adhesion and WNT signaling. Omayma, Jobana and Jenny will work under the supervision of Renee on projects that are more data analysis driven. Using online tools and existing datasets, they will generate new hypotheses for follow up research in the lab - all with the goal of gaining a better understanding of tissue-specific initiation and interpretation of WNT/CTNNB1 signaling.

As a joint side project, the goal is to also make a lab wiki highlighting and describing these online tools and workflows.

2 February, 2021

Thijs joins the lab as a new staff scientist

Thijs van Boxtel started in the lab today. He will split his time as an assistant professor between research and teaching and brings with him many years of experience in developmental biology.

Welcome Thijs!

1 February, 2021

Announcing the start of our artist in residence program

(ENG)
We are excited to officially announce the start of our lab’s artist-in-residence program.

As this week is our National Poetry Week, this is also a fitting moment to introduce our first affiliated artist, Dutch poet Rosa Schogt.

It is our long-term goal to embed one new artist in our lab for a period of 6-12 months every calendar year and hopefully we can raise sufficient funds to ensure continuity. We aim to offer an inspiring environment - the rest is up to the artist.
Do you think you might be interested in becoming our next artist in residence? Do you want to support this effort financially? Then go ahead and contact Renée for more information.


(NL) We zijn blij dat we eindelijk de officiële start van ons artist-in-residence programma kunnen aankondigen. We hopen dat we in de toekomst op structurele basis kunstenaars van divers pluimage (schrijvers, schilders, beeldhouwers, performance artists) voor een periode van 6-12 maanden een inspirerende omgeving kunnen bieden.

Met veel trots introduceren we de eerste kunstenaar die tot en met december aan ons lab verbonden zal zijn: dichter Rosa Schogt, die in 2019 debuteerde met haar bundel "Dansen te ontspringen".
Deze aankondiging komt, alsof het zo gepland is, midden in de Poëzieweek, die als thema "samen" heeft. We hopen dat er in de komende maanden inderdaad een mooie verbinding gaat ontstaan tussen kunst en wetenschap.

Heb jij interesse om onze volgende artist-in-residence te worden? Of wil je dit initiatief financieel steunen? Neem dan contact op met Renée voor meer informatie.

Bekijk het optreden van Rosa Schogt tijdens de nacht van de poëzie, die zij in 2019 mocht afsluiten:


Dit schreef de Volkskrant over Rosa’s debuut bundel:

30 January, 2021

Happy Holidays

We are taking a short break for the Christmas holidays!

24 December, 2020

Mini college recorded

In between re-organizing the lab, wrapping up before Christmas and juggling the pandemic, Renée recorded a mini college on stem cells and cancer (in Dutch) in the FNWI recording studio.

It is now available at the Open Huis website.

Usually this is part of the "Bachelor Voorlichtingsdagen" for interested high school students and their parents, but these events too could, unfortunately, not be held in real life this year.

15 December, 2020

Review article on CTNNB1 published

Our review on CTNNB1, written by Tanne and Renée, came out today as an Open Access article in Open Biology.

You can access it here, or you can go straight to the PDF by clicking here.

So head on over to the Royal Society (that does make one feel like a 17th/18th century scholar, doesn’t it) to read "Walking the tight wire between cell adhesion and WNT signalling: a balancing act for beta-catenin". You know you want to!

9 December, 2020

Paper accepted

Our paper "How to use online tools to generate new hypotheses for mammary gland biology research: a case study for Wnt7b", previously available as a pre-print, has found a permanent home in the Journal of Mammary Gland Biology and Neoplasia.

Congratulations to Yorick and Nika!

25 November, 2020

Review accepted

Today we celebrated that Tanne’s review article on the dual function of CTNNB1 in cell adhesion and WNT signaling was accepted for publication in Open Biology.

Scientific details will follow as soon as the link to the final PDF is available. For now, we are happily awaiting the proofs and enjoying this bit of tangible output of working from home in the midst of a pandemic.

Congratulations Tanne!

19 November, 2020

Recruiting a staff scientist

We are recruiting a staff scientist (UD level, assistant professor). This is a non-tenure track position (50/50 teaching/research).

For details, see the official vacancy at the UvA website or over at Academic Transfer.

The deadline for applying is 7 December 2020 and we hope to still interview candidates before the Christmas break. You can contact Renée for more information.

9 November, 2020

The lab gets an official name

Amidst all of the COVID-19 craziness, 2020 also brought an exciting highlight:

The lab got an official name and now forms the Developmental, Stem Cell and Cancer Biology (DSCCB) research group in the Cell & Systems Biology cluster of the Swammerdam Institute for Life Sciences.

We still refer to ourselves as "the Wntlab" because it rolls off the tongue a bit easier.

24 October, 2020

Celebrating things worth celebrating - COVID style

We had planned to celebrate the start of Ingeborg’s appointment with a lab lunch in the Polder, but the Dutch Coronvirus measures got tightened - so those plans had to be cancelled and we had to improvise.

Our N=6 was just small enough to fit into the SILS common room at a safe social distance and all snacks were safely and properly aliquoted into individual portions.

Shortly after, the Corona protocol got updated and the rules got tightened even further, so we can now only do social experiments with a max. of N=4, unfortunately. Which only goes to show that you have to seize an opportunity when it presents itself!

8 October, 2020

Tanne and Renée talk about breasts on Radio Swammerdam

October is breast cancer awareness month - a very good reason for Radio Swammerdam to focus their weekly hour of science radio on the breast.
Tanne hosted the broadcast on Sunday morning 4 October and Renée joined as a guest. If you missed it, you can listen to the Radio Swammerdam podcast:

4 October, 2020

Ingeborg joins the lab as a new technician

We welcome Ingeborg Hooijkaas, who joined the lab on 1 October as our new technician.

Despite the pandemic, and with lots of us still spending considerable amounts of our time working from home, we hope that Ingeborg will quickly feel at home and be able to get up and running in the lab. Hopefully it will not be too long before she can get to meet all of her SILS colleagues face to face.

1 October, 2020

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