Hugo received new funding from KWF (€820k), the Dutch Cancer Foundation, to strengthen our team with two new PhD students. We will use this support to make a deep dive into the tumor microenvironment of invasive fronts at the earliest stages of colorectal cancer formation.
Hugo received a prestigious ERC consolidator grant (€2,0M) from the EU in support of our studies to understand the evolution of the tumor genome during the earliest formation of colon cancer. The project will rely heavily on genome analysis at the single-cell level in both tumors and multi-regional organoid derivatives that are representatives for sequential steps in tumor progression (being normal, adenoma, cancer and invasive front). Needless to say, we will make many fluorescent knock-in & knock-out organoids, because that’s what we like 🙂
Beautiful ceremony in the Amsterdam Stedelijk Museum for modern art. AMMODO Science Award is a biannual prize for early-career scientists to continue their research line as they seem fit (€350k).
Proud to be listed among all previous recipients. Thankful to all current and past team members, and colleagues in the CMM department.
See a short video below about my team’s current interests:
Drug-resistant cells are often metabolically inactive, compromising the suitability of mostly used drug response assays on organoids. In this publication @Cell reports, we designed a novel microscopy-based drug screen that accurately distinguishes dead from alive organoids. We found microtubule-targeting agents, commonly used in clinical oncology, to eliminate RAS mutant cells resistant to effective MAPK pathway inhibition.
Superior work from Sander!!! now being tested in a clinical trial!!!
Excited that Oncode Institute will continue to support fundamental research in our fight against cancer. Needless to say, we are proud to remain a member (senior now) and ready to roar!
Maria Heinz successfully defended her thesis called ‘Cellular heterogeneity during metastatic colonization of colorectal cancer’. Her thesis was a tour de force at a complex topic, but she excellent and showed great expertise of the topic and science in general. Both her social coffee glue and intellect will be missed. We wish her all the best in her further career and life in Heidelberg, Germany.
Yannik successfully defended his thesis called ‘Karyotype diversification in colorectal cancer’. His PhD trajectory was co-supervised by Prof. dr. Leon Terstappen of the University of Twente. Yannik will continue to pursue his interest in CRISPR editing of patient models within the infrastructure of Roche Institute for Translational Bioengineering (Basel, Switzerland). We wish him all the luck, and not only at his beloved poker table!
Ever wondered what the cellular trajectory is of a cancer cell metastasizing to the liver? Maria finished a tour de force @Cancer Research, mapping shapeshifting cancer stem cell phenotypes with high precision during metastasis formation.
Ooh…, regarding epithelial self-organization in organoids: it is conserved between mice, human, normal and cancer organoids. Its clinical relevance: the exact same processes take place during liver metastasis formation in patients.
Super happy with this technology, foremost as we now can make (complex) knock-ins in human organoids on weekly basis. Major advantages are no off-targets. As a consequence, you can pool all knock-in cells to expedite culture expansion and/or maintenance of polyclonality (in case of tumors). Targeting vectors enable one-step cloning (and all are available @Addgene).
Overall result, amazing looking knock-in organoids within 2wks! @PLOS BIOLOGY
Proud on this fantastic publication in Nat Genet. We established 3D Live-Seq: the integration of live-cell imaging of tumor organoids and whole-genome sequencing of each imaged cell. Combined, these super powerful technologies enable the exact reconstruction how evolving tumor genomes change and mutate over consecutive cell generations. Mapping the tempo and rate of genome alterations identified punctuated and gradual patterns.
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I am one of the thankful recipients of the NWO VIDI grants 2021 (Dutch Research Council). VIDIs are for early career scientist to launch their successful independent research track to the next level. I will use this funding to explore the early-stages of colon cancer, among others to improve recognition of early metastatic cancers.
Wow, so excited about this work that reads like a trilogy. First, we re-engineered a fluorescent FRET biosensor for ERK into an improved version EKAREN5 (available at Addgene). Second, we established quantitative real-time ERK-FRET measurements in all tumor cells of drug-challenged organoids. As last, we reveal that upstream EGFR activity matters in tumors, even in the presence of mutant KRAS or BRAF, being a rigorous amplifier of intrinsically limited oncogene-driven signaling.
Much delayed by COVID, but Lotte was finally allowed to defend her thesis. Opponents and guests were virtually present, while Lotte filled the empty room with great display of her expertise and knowledge!
Yes, he is different! We welcome the first MD in our group! Maarten will carry out a phase1/2 trial to test a new therapy against KRAS mutant colon cancer. In parallel he will test organoids as companion diagnostics. Maarten will be co-supervised by Jeanine Roodhart, medical oncologist in our hospital.
COVID lockdown provided a window to reexamine current literature regarding stem cell function and environmental control. Joris took the lead and shaped his long-term interest into a new review.
Lotte publishes experimental data in Cell reports that the number of functional stem cells increases in intestinal crypts upon caloric restriction, confirming prior studies using marker gene expression.
Most of our lab work has been restricted since half of March. After about two months, we are enthusiastic to slowly reopening the labs. Virtual meetings are likely to stay in some sort…
Thankful for our great and long-lasting collaboration with the Van Rheenen laboratory! New work, spearheaded by the Van Rheenen lab, in Cell Stem Cell about the origin of liver metastases from colorectal cancers. Using genetic mouse models and intravital imaging, it turns out that the major suspects, i.e. so-called cancer stem cells, are not the predominant seeders of metastases.
Hugo is a member of a multidisciplinary research team (AMOLF, NKI, Hubrecht & UMCU) that successfully applied for a NWO groot research grant (~€2,5M). The team will perform functional studies on rare cell types in the gut to delineate their relationship with common diseases like Crohn’s, obesity, infections or irritable bowel syndrome.
We wrote a review about the types of oncogenic mutations in the MAPK pathway in colorectal cancer. They are similar but different. Unfortunately, studying them is often comparing apples to oranges. Organoid models and CRISPR genome editing might pave the way…
Michiel was awarded a prestigious Marie Curie research grant to continue his science in our lab after an earlier successful period at MSKCC in NY, USA. Well done! Michiel will study genetic alterations in esophageal adenocarcinoma using patient organoids and high-end imaging.
Jasmin successfully defended her thesis called ‘Similar but different: Oncogenic MAPK pathway mutations in colorectal cancer’. Jasmin is fully prepared to take on the business world. We wish her all the luck in her career and life.
We welcome two new PhD students to our team, J&J.
As students, Julian and Joris have both been matured in our lab, with their grand finales at Rockefeller University (NY) and University of Cambridge (UK) respectively.
Proud to be one of the seven projects in the Organ-on-Chip Showcases call that have been awarded a grant by Top Sector Life Sciences & Health (Health~Holland). I will continue to explore the use of microfluidics (from industrial partner VyCAP) with live-cell imaging of organoids to study tumor evolution.
Koen successfully defended his thesis called ‘Cell fate dynamics in intestinal homeostasis and cancer’. He is now gone to the lab of Jacco van Rheenen (NKI, Amsterdam) in preparation to his upcoming adventure in the lab of Prisca Liberali (FMI, Basel). We wish him all the luck in science and life.
Our collaborative study with the Kops laboratory is published in Nature Genetics. We performed detailed live-cell microscopy on patient-derived tumor organoids from colorectal cancer patients, to study chromosomal instability levels and cell fate options after erroneous divisions in correlation to karyotype evolution. Among others we show that chromosomal instability is prevalent and ongoing in CRCs, including those designated as hypermutated (microsatellite instable). Great work by Ana and Bas.
Fantastic work from the Kloosterman and Clevers laboratories in Nature Medicine about the development of a new platform for the culture of ovarian cancer organoids. Nizar worked hard on the drug screening of these organoids to support the claim that these organoids can assist in personalized therapy design as well as drug development in a pre-clinical setting.
Our new study is published in Oncotarget, featuring a CRISPR-screen to test the impact of RASGAP deficiencies on anti-EGFR therapy-resistance in colorectal cancer. Fantastic work by Jasmin to make genetic knock-out organoids and optimize biochemical analysis of the MAPK pathway in these models
Together with the laboratories of Madelon Maurice and Onno Kranenburg, we received a TOP grant of €675k from ZonMW, the Netherlands Organization for Health Research and Development. We aim to understand why seemingly identical combinations of genetic alterations (mutations) can lead to different forms of colorectal cancer in terms of aggressiveness and therapy-resistance.
We welcome 2 new Postdocs to join our team.
Michiel Boekhout finished his first postdoc at MSKCC in NY, USA, studying double-strand break formation in DNA during meiosis (Keeney lab).
Suzanne van der Horst studied stem cells in C. elegans using real-time imaging and CRISPR-mediated genetic knock-ins (Van den Heuvel lab, UU).
Petra van Leenen finished her bachelors at the Hogeschool Utrecht after a successful internship in our lab. She will stay as a research technician.
Hugo received a prestigious ERC starting grant (€1,5M) from the EU in support of our studies to understand the cause and consequence of diverging behaviors between different tumor cell types. The project will rely heavily on real-time monitoring of cell type specification in tumors (organoids), as well as quantitative measurements of signaling activities at the single-cell level.
Integrated multi-omics analyses of organoid model systems to study lineage specification in the intestinal epithelium (Mol Syst Biol). Great work, spearheaded by the lab of Michiel Vermeulen, RIMLS, Nijmegen.
Together with the laboratories of Young Seok Ju (KAIST, Daejeon, SK) and Bon-Kyoung Koo (IMBA, Vienna, Austria), we received a Young Investigator grant ($1M) from the Human Frontier Science Program. We will study hyper mutagenesis on the course of tumor evolution in gastric cancers.
Official launch of Oncode Institute. The institute will support fundamental research in our fight against cancer. Hugo is proud to be a founding scientist of Oncode as junior investigator.
We developed and validated a synthetic enhancer/promoter element that provides specific transcriptional activity in intestinal stem cells. The reporter, called STAR, is a user-friendly system to monitor and manipulate stem cells in human organoids. Among others, we documented that cell fate plasticity in tumors is an inherited trait from normal cells, rather than acquired by specific cancer mutations.
Using intravital imaging technology that is developed and performed in the lab of Jacco van Rheenen (NKI), Lotte identified that neighboring crypts (stem cell compartments in the gut) can fuse together. The fusion process looks almost identical to crypt fission (splitting in two) but is in the reverse direction, presumably explaining why fusion has never been picked up before.