Areas of expertise uitklapper, klik om te openen
Dr. Hugo Snippert is Group Leader at the department of Molecular Cancer Research within the Center of Molecular Medicine at the University Medical Center Utrecht.
Hugo received his PhD (cum laude) in the lab of Hans Clevers (Hubrecht Institute) where he used advanced mouse genetics and microscopy to characterize (new) stem cell populations in the mouse intestine, skin and intestinal cancer. Moreover, he was closely involved in the establishment of the first organoid culture system (mini-organs in a dish).
After a brief postdoc at the Kavli Institute of Nanoscience (Delft University of Technology) on cutting edge microscopic technologies, he initiated his own research line in the MCR department of the UMC Utrecht to understand heterogeneity in (stem) cell behavior during tumor formation and cancer progression. In 2016, he became group leader in the MCR department, where his group exploits the unique combination of I) primary human cancer samples (tumor organoids), II) molecular genetics to engineer and manipulate human cancers and III) real-time imaging to monitor and quantify cellular behavior to study phenotypic heterogeneity between cancer cells, with the long term goal to understand and prevent therapy resistance in cancer.
Multicolor lineage tracing with Confetti elegantly illustrates the strength of combining molecular genetics and microscopy to facilitate the understanding of stem cell behavior in the mouse intestine (Snippert et al., Cell 2010)
Read the double interview about a career in science with Hugo and Hans Clevers (in Dutch).
Research program/group uitklapper, klik om te openen
Phenotypic heterogeneity in cancer
Cells within a cancer are highly heterogeneous with respect to their phenotype and can manifest distinct morphological, molecular and functional features. As a consequence, it is challenging to design treatment therapies that target all cancer cells as effectively.
The Snippert group studies heterogeneity of cellular behavior during cancer growth and therapy resistance in human cancer samples. Among others, we want to identify and characterize the origin and nature of the resistant cells that give rise to cancer recurrence.
Patient-derived tumor organoids
In the Snippert group we mainly use patient-derived colorectal cancer organoids to study cellular phenomena that have a large impact on human cancer (treatment), such as therapy resistance. Most importantly, cancer organoid cultures can be established from virtually all cancer types, thereby allowing us to study phenomena across many different tumor subtypes, cancer stages and mutational landscapes that are present within the patient population.
Molecular genetics to engineer tumor organoids
In addition, we apply molecular genetics to engineer the cancer organoids to our own interest, which includes CRISPR/Cas9-mediated homologous recombination to introduce or correct cancer mutations at their exact endogenous location.
Alternatively, we introduce reporters to monitor and/or manipulate cellular processes in real-time that underlie the plasticity of cellular identities and behavior during tumor growth and therapy resistance.
Real-time microscopy at subcellular resolution
Our group develops and utilizes state-of-the-art imaging techniques to visualize the cellular behavior of individual cancer cells within human cancer samples. We integrate sensors and biomarkers to monitor and quantify cellular identities and signaling activities on a cellular level in real-time.
We develop real-time imaging technology to monitor cellular behavior in colorectal cancer organoids at high temporal and spatial resolution. In this example H2B-labeled nuclei are visualized with a color-coded depth of maximum-projected z-stacks. Among others, we have been using these techniques to quantify chromosomal instability in engineered tumor organoids (Drost et al., Nature, 2015).
Group members uitklapper, klik om te openen
- Bas Ponsioen - Postdoc
- Koen Oost - PhD student
- Jasmin Post - PhD student
- Lotte Bruens - PhD student (shared with J. van Rheenen, Hubrecht Institute)
- Maria Heinz - PhD student
- Yannik Bollen - PhD student (shared with L. Terstappen, MIRA/UT)
- Ingrid Verlaan - Technician
- Sander Mertens - Technician
- Nizar Hami - Technician
Key publications uitklapper, klik om te openen
- Oost KC, van Voorthuijsen L, Fumagalli A, Lindeboom RGH, Sprangers J, Omerzu M, Rodriguez-Colman MJ, Heinz MC, Verlaan-Klink I, Maurice MM, Burgering BMT, van Rheenen J, Vermeulen M, Snippert HJG#. Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene. Cell Rep 2018
- Bruens L, Ellenbroek SIJ, van Rheenen J, Snippert HJ#. In vivo Imaging Reveals Existence of Crypt Fission and Fusion in Adult Mouse Intestine. Gastroenterology 2017
- Verissimo CS, Overmeer RM, Ponsioen B, Drost J, Mertens S, Verlaan-Klink I, Gerwen BV, van der Ven M, Wetering MV, Egan DA, Bernards R, Clevers H, Bos JL, Snippert HJ#. Targeting mutant RAS in patient-derived colorectal cancer organoids by combinatorial drug screening. eLIFE 2016
- Drost J, van Jaarsveld RH*, Ponsioen B*, Zimberlin C*, van Boxtel R, Buijs A, Sachs N, Overmeer RM, Offerhaus GJ, Begthel H, Korving J, van de Wetering M, Schwank G, Logtenberg M, Cuppen E, Snippert HJ, Medema JP, Kops GJ, Clevers H. Sequential cancer mutations in cultured human intestinal stem cells. Nature 2015
- Vermeulen L# and Snippert HJ#. Stem cell dynamics in homeostasis and cancer of the intestine. Nat Rev Cancer 2014
- Snippert HJ*#, Schepers AG*, Van Es JH, Simons BD, Clevers H#. Biased competition between Lgr5 intestinal stem cells driven by oncogenic mutation induced clonal expansion. EMBO Rep 2014
- Schepers AG*, Snippert HJ*, Stange DE, van den Born M, van Es JH, van de Wetering M, Clevers H. Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas. Science 2012
- Snippert HJ, Van der Flier LG, Sato T, Van Es JH, Van den Born M, Kroon-Veenboer C, Barker N, Klein AM, Van Rheenen J, Simons BD, Clevers H. Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells. Cell 2010
- Snippert HJ*, Haegebarth A*, Kasper M, Jaks V, van Es JH, Barker N, van de Wetering M, van den Born M, Begthel H, Vries RG, Stange DE, Toftgård R, Clevers H. Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin. Science 2010
- Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala P, Peters PJ, Clevers H. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 2009
More contact information uitklapper, klik om te openen
Stratenum, room number 3.231
3584 CG Utrecht
Marianne van der Heiden
+31 (0)88 75 68989