UMC 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 pioneered live-cell imaging of stem cell behavior within the first organoid models (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 functional heterogeneity between phenotypic and genetically diverse cancer cells, with the long term goal to understand and prevent cancer occurrence and therapy resistance.

• 2013: NWO-Veni

• 2015: Martinus van Marum Prize, Koninklijke Hollandsche Maatschappij der Wetenschappen

• 2018: ERC starting grant

• 2018: HFSP young investigators grant

• 2021: NWO-Vidi

• 2023: AMMODO science award

• 2023: ERC Consolidator grant

1. Heinz MC, Peters NA, …, Kranenburg O, Snippert HJG. (2022). Liver Colonization by Colorectal Cancer Metastases Requires YAP-Controlled Plasticity at the Micrometastatic Stage.Cancer Res. 16;82(10):1953-1968.

2. Bollen Y, Stelloo E, …, Snippert HJG. (2021). Reconstructing single-cell karyotype alterations in colorectal cancer identifies punctuated and gradual diversification patterns. Nat Genet. 53(8):1187-1195.

3. Ponsioen B, …, Snippert HJG. (2021). Quantifying single-cell ERK dynamics in colorectal cancer organoids reveals EGFR as an amplifier of oncogenic MAPK pathway signalling. Nat Cell Biol. 23(4):377-390.

4. Bolhaqueiro ACF, Ponsioen B, …, Snippert HJG, Kops GJPL. (2019). Ongoing chromosomal instability and karyotype evolution in human colorectal cancer organoids. Nat Genet.51(5):824-834.

5. Verissimo CS, Overmeer RM, Ponsioen B, …, Snippert HJ. (2016). Targeting mutant RAS in patient-derived colorectal cancer organoids by combinatorial drug screening. eLIFE, 15;5:e18489.

As a result of my training at both the Netherlands Cancer Institute and the Delft University of Technology, I am a bioinformatics scientist with a solid background in computational data science and a strong desire to improve cancer genomics. My research focuses on creating cutting-edge machine-learning-inspired methods to increase the knowledge that can be retrieved from cancer patient omics data.

Cancer research increasingly relies on complex(big)data that capture multiple aspects of the same patient or sample. As a result, bioinformatics expertise becomes indispensable to i) provide data analytics methods that enable extracting relevant knowledge from the data, ii) create data integration methods to further our understanding of the complex interplay between biological variables and iii) facilitate FAIR data management to promote reproducibility and data sharing. My research group aims to address all three of these aspects.

• 2022: Oncode TechDev study on applying Sturgeon, an deep-learning based methylation classifier for perioperative brain cancer classification

• 2018: Oncode Clinical Proof of Concept study on applying CyclomicsSeq for Head and Neck Cancer (with Kloosterman)

• 2017: NIH-4D Nucleome TCPA (de Laat lab)

• NWO Veni (2012) and NWO Vidi (2017) recipient

1. A Marcozzi, M Jager, ..., W Kloosterman*, J de Ridder*, Accurate detection of circulating tumor DNA using nanopore consensus sequencing, NPJ Genomic Medicine, 20212,

2. M Nieboer and J de Ridder*, svMIL: Predicting the pathogenic effect of somatic structural variants through multiple instance learning, Bioinformatics, 20203.

3. J Ubels, T Schaefers, C Punt, H Guchelaar and J de Ridder*, RAINFOREST: A random forest approach to predict treatment benefit in data from (failed) clinical drug trials, Bioinformatics, 2020

4. A Allahyar and C Vermeulen, ..., J de Ridder*, W de Laat*, Enhancer hubs and loop collisions identified from single-allele topologies. Nature Genetics, 2018. PMID: 29988121

5. FJ Rang, WP Kloosterman*, J de Ridder*, From squiggle to basepair: computational approaches for improving nanopore sequencing read accuracy. Genome Biology, 2018. PMID: 30005597

6. J Ubels, P Sonneveld, EH van Beers, A Broijl, MH van Vliet*, J de Ridder*, Predicting treatment benefit in multiple myeloma through simulation of alternative treatment effects. Nature Communications, 2018. PMID: 30054467

Linde Meyaard finished her undergraduate studies in Biomedical Sciences at Leiden University in 1990. She next studied T cell function in HIV-1 infection with Frank Miedema at Sanquin in Amsterdam, where she obtained her PhD in 1995. As post-doctoral fellow, she started studying immune inhibitory receptors with Joseph Phillips and Lewis Lanier at DNAX research institute in Palo Alto, CA. Upon return to the Netherlands she continued her work on inhibitory immune receptors in the lab of Hans Clevers and developed into an independent group leader at the University Medical Center in Utrecht.

Meyaard was appointed full Professor of Immune Regulation in Utrecht in 2007. Her work is supported by several prestigious grants, such as a fellowship of the Royal Dutch Academy of Sciences (1999-2001) and personal grants from the Dutch society for Scientific Research (2001, 2002 and 2014) and by grants from the Dutch Arthritis Foundation, Dutch Cancer Society, AICR and others.

The growing interest in her expertise on targeting inhibitory receptors therapeutically resulted in collaborations with pharmaceutical companies. Meyaard serves on multiple scientific boards and was secretary general of the Dutch Society of Immunology from 2008-2014. She spent the 2016-2017 year as a visiting scientist in the lab of Ruslan Medzhitov at the department of Immunobiology at Yale University, New Haven, CT.

• 2014: NWO Vici

• 2002: NWO Aspasia

• 2001: NWO Vidi

• 1999: Fellow of the Royal Dutch Academy of Science (KNAW)

• 1995: Cum Laude for PhD

1. Geerdink, R. J., Hennus, M. P., Westerlaken, G. H., Abrahams, A. C., Albers, K. I., Walk, J., ... & Meyaard, L. (2017). LAIR-1 limits neutrophil extracellular trap formation in viral bronchiolitis. Journal of Allergy and Clinical Immunology.

2. Lebbink, R. J., de Ruiter, T., Adelmeijer, J., Brenkman, A. B., van Helvoort, J. M., Koch, M., ... & Meyaard, L. (2006). Collagens are functional, high affinity ligands for the inhibitory immune receptor LAIR-1. Journal of Experimental Medicine, 203(6), 1419-1425.

3. Rygiel, T. P., Karnam, G., Goverse, G., Van Der Marel, A. P. J., Greuter, M. J., Van Schaarenburg, R. A., ... & Mebius, R. E. (2012). CD200-CD200R signaling suppresses anti-tumor responses independently of CD200 expression on the tumor. Oncogene, 31(24), 2979.

4. Van Avondt, K., van der Linden, M., Naccache, P. H., Egan, D. A., & Meyaard, L. (2016). Signal inhibitory receptor on leukocytes-1 limits the formation of neutrophil extracellular traps, but preserves intracellular bacterial killing. The Journal of Immunology, 196(9), 3686-3694.

5. Van Der Vlist, M., Kuball, J., Radstake, T. R., & Meyaard, L. (2016). Immune checkpoints and rheumatic diseases: what can cancer immunotherapy teach us?. Nature Reviews Rheumatology, 12(10), 593.

Madelon Maurice earned her PhD in 1998 at the Department of Rheumatology, LUMC, Leiden, the Netherlands on T-cell mediated autoimmunity. She performed postdoctoral training in the laboratories of Hidde Ploegh, Harvard Medical School, Boston, USA, and Hans Clevers, Hubrecht Institute, Utrecht, gaining expertise in a diverse set of disciplines. She initiated her independent research group in 2006 at the department of Cell Biology, UMC Utrecht and became Full Professor of Molecular Cell Biology in 2016. Her primary research interests concern the molecular mechanisms by which (mutated) signalling pathways guide cell-cell communication, tissue self-organization and tumour growth and progression.

The innovative nature of her work was recognized with an Utrecht High Potential grant (2007), ERC Starting grant (2009), NWO-VICI grant (2014), ZonMW-TOP grant (2018) and a KWF/TKI grant (2022). Madelon is one of the main leaders of the national Gravitation project IMAGINE! (https://imagine-microscopy.nl). She is an elected member of the Bijvoet Center for Biomolecular Research and has been a member of the Young Academy of Europe (YAE) (2014-2019). From 2013-2017, Madelon coordinated the Marie Curie Sklowdowska EU ITN consortium “WntsApp”, that comprised 7 academic and 3 private sector European partners (wntsapp.eu) that joined forces to uncover molecular aspects of WNT receptor signal relay and develop therapeutics to interfere with aberrant WNT signaling in cancer cells. She is a member of the Research Management Committee of the Oncode Institute, Co-director of the Utrecht Platform for Organoid Technology (U-PORT), member of the Scientific Council of the Dutch Cancer Society and has been member of the Program Council of the Utrecht Life Sciences (ULS) Board (2017-2021).

Madelon invented a novel strategy for targeted membrane protein degradation using bispecific antibodies (SureTACs). She is founder and shareholder of Laigo Bio, a startup biotech that aims to develop SureTACs for clinical application in cancer treatment (laigobio.com).

• 2022: KWF/TKI grant

• 2022: Gravitation grant IMAGINE! (one of the main applicants)

• 2018: NWO TOP grant

• 2015: NWO VICI grant

• 2012: ERC PoC grant

• 2009: ERC Starting grant

1. Bugter JM, Fenderico N, Maurice MM. Mutations and mechanisms of WNT pathway tumour suppressors in cancer (2020). Nat Rev Cancer.Jan;21(1):5-21. doi: 10.1038/s41568-020-00307-z. Epub 2020 Oct 23.PMID: 33097916

2. Spit M, Fenderico N, Jordens I, Radaszkiewicz T, Lindeboom RGH, Bugter, JM, Cristobal A, Ootes L, van Osch M, Janssen E, Boonekamp KE, Hanakova K, Potesil D, Zdrahal Z, Boj SF, Medema JP, Bryja V, Koo, BK, Vermeulen M, Maurice MM. RNF43 truncations trap CK1 to drive niche-independent self-renewal in cancer (2020). EMBO J. Sep 15;39(18):e103932. doi: 10.15252/embj.2019103932.

3. Fenderico N, van Scherpenzeel RC, Goldflam M, Proverbio D, Jordens I, Kralj T, Stryeck S, Bass TZ, Hermans G, Ullman C, Aastrup T, Gros P, Maurice MM. Anti-LRP5/6 VHHs promote differentiation of Wnt-hypersensitive intestinal stem cells (2019) Nat Commun.10(1):365. doi: 10.1038/s41467-018-08172-z.

4. Anvarian Z, Nojima N, van Kappel E, Madl T, Spit M, Viertler M, Jordens I, Low TY, van Scherpenzeel R, KuperI, Richter K, Heck AJR, Boelens R, Vincent JP, Rüdiger SGD, Maurice MM. Axin cancer mutants form nanoaggregates to rewire the Wnt signalling network (2016) Nat Struct Mol Biol. (2016) Apr;23(4):324-32. doi: 10.1038/nsmb.3191.

5. Koo, B. K., Spit, M., Jordens, I., Low, T. Y., Stange, D. E., van de Wetering, M., van Es J, Mohammed S, Heck AJ, Maurice MM^#, Clevers, H^#. (2012). Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors. Nature 488(7413), 665.(^#co-corresponding)

Susanne Lens obtained her PhD in 1998 at the University of Amsterdam (René van Lier and Rien van Oers) for her studies on the role of CD27-CD70 interactions in normal and malignant B cell growth and differentiation, and on the signaling pathways leading to B-cell antigen receptor induced apoptosis. She then joined the lab of Jürg Tschopp, University of Lausanne, Switzerland to perform her postdoctoral studies on apoptosis inhibitors. In 2001 she changed research fields to gain expertise in cell cycle biology in the lab of René Medema, at the Netherlands Cancer Institute in Amsterdam, which resulted in her research line on the Chromosomal Passenger Complex and the regulation of chromosomal stability. She was appointed as Associate Professor within the department of Medical Oncology of the UMCU in 2006 and was awarded a Full Professorship on Genome Instability in 2013. Her primary research interests involve the molecular mechanisms that ensure error-free propagation of the genome during cell division, how defects in these mechanisms contribute to chromosomal instability in cancer, and how recurrent aneuploidy patterns in cancer arise and contribute to disease development.

• 2011: Laureate of NWO Innovational Research Incentives Scheme

• 2005: Laureate of NWO Innovational Research Incentives Scheme

• 1999: Fellow of the Dutch Cancer Society

1. Adriaans IE, Hooikaas PJ, Aher A, Vromans MJ, van Es RM, Grigoriev I, Akhmanova A, Lens SM. (2020). MKLP2 Is a Motile Kinesin that Transports the Chromosomal Passenger Complex during Anaphase. Current Biology, 30:2628.

2. Hadders MA, Hindriksen S, Truong MA, Mhaskar AN, Wopken JP, Vromans MJ, Lens SM (2020). Untangling the contribution of Haspin and Bub1 to Aurora B function during mitosis. J. Cell Biol. 219: e201907087.

3. Lens SM & Medema RH (2019). Cytokinesis defects and cancer. Nature Rev. Cancer, 19: 32.

4. Hengeveld RC, Vromans MJ, Vleugel M, Hadders MA & Lens SM (2017). Inner centromere localization of the CPC maintains centromere cohesion and allows mitotic checkpoint silencing. Nature Communications, 8: 15542.

5. Liu D, Vader G, Vromans MJ, Lampson MA, & Lens SM (2009). Sensing chromosome bi-orientation by spatial separation of aurora B kinase from kinetochore substrates. Science, 323: 1350.

Wouter de Laat performed his PhD (1998) at the Erasmus University Rotterdam (Prof. Jan Hoeijmakers) where he investigated the molecular mechanism of nucleotide excision repair. He identified one of the nucleases and characterized the interplay between repair factors at the site of the lesion. As a postdoc, he joined the group of Prof. Frank Grosveld to work on beta-globin gene activation. In 2000 he received a career grant (VIDI) to work on long-range gene activation. His group used 3C technology, and later developed 4C technology, to demonstrate chromatin loops between genes and enhancers and to uncover the principles and functional importance of long-range DNA contacts within and between chromosomes.

In September 2008 de Laat moved his group to the Hubrecht Institute, where he continued his work on genome structure and function and further pioneered the development and application of 3C-based technologies in DNA diagnostics. In January 2009 he was appointed professor in Biomedical Genomics at the University Medical Center Utrecht. Wouter de Laat is founder of Cergentis, a biotech company now owned by Solvias, that provides services and kits for complete gene sequencing based on its proprietary Targeted Locus Amplification (TLA) Technology.

• 2019: Prix Galien Excellence COVID-19 Award

• 2012: VICI career grant

• 2009: Elected EMBO member

• 2008: ERC Starting Grant

• 2000: VIDI career grant

1. Rinzema NJ, Sofiadis K, Tjalsma SJD, Verstegen MJAM, Oz Y, Valdes-Quezada C, Felder AK, Filipovska T, van der Elst S, de Andrade Dos Ramos Z, Han R, Krijger PHL, de Laat W. (2022). Building regulatory landscapes reveals that an enhancer can recruit cohesin to create contact domains, engage CTCF sites and activate distant genes. Nat Struct Mol Biol. 29(6):563-574

2. Krijger PHL, Hoek, TA, Boersma S, Donders LIPM, Broeders MCM, Pieterse M, Toonen PW, …, van Weert A, Dekker E, Dom FJ, Ruijtenbeek R, van der Velden LBJ, van de Bovenkamp JHB, Bosch M, de Laat W, Tanenbaum ME. (2021). A public-private partnership model for COVID-19 diagnostics. Nat Biotech 39(10):1182-1184.

3. Vos ESM, Valdes-Quezada C, Huang Y, Allahyar A, Verstegen MJAM, Felder A-K, van der Vegt F, Uijttewaal ECH, Krijger PHL, and de Laat W (2021). Interplay between CTCF boundaries and a super enhancer controls cohesin extrusion trajectories and gene expression. Mol Cell, Jun 22:S1097-2765(21)00455-X.

4. Allahyar A, Pieterse M, Swennenhuis J, Los-de Vries GT, Yilmaz M, Leguit 4, Meijers RWJ, van der Geize R, Vermaat J, Cleven A, van Wezel T, Diepstra A, van Kempen LC, Hijmering NJ, Stathi P, Sharma M, Melquiond ASJ, de Vree PJP, Verstegen MJAM, Krijger PHL, Hajo K, Simonis M, Rakszewska A, van Min M, de Jong D, Ylstra B, Feitsma H, Splinter E, de Laat W. (2021). Robust detection of translocations in lymphoma FFPE samples using Targeted Locus Capture-based sequencing. Nat Comm. 7;12(1):3361.

5. Allahyar A, Vermeulen C, Bouwman BAM, Krijger PHL, Verstegen MJAM, Geeven G, van Kranenburg M, Pieterse M, Straver R, Haarhuis JHI, Jalink K, Teunissen H, Renkens IJ, Kloosterman WP, Rowland BD, de Wit E, de Ridder J, de Laat W. (2018). Enhancer hubs and loop collisions identified from single-allele topologies. Nat Genet. 50(8):1151-1160.

Boudewijn Burgering is a Professor in Signal Transduction and head of the Center Molecular Medicine (CMM) and head research of the section Molecular Cancer Research of the CMM at the UMCU. Boudewijn is also head of the Graduate School Cancer, Stem Cells and Development (CSnD), a visiting scientist to NCBS/InStemm Institute in Bangalore and a visiting Professor Second College of Clinical Medicine of Guangzhou, China. Boudewijn is running together with Prof Dr Nanda Verhoeven Duif the Utrecht Centre for Medical Metabolomics that provides services and expertise to researchers that wish to study metabolism within the context of their research. Also at MCR proteins@work is located, which provides support in proteomics for the UMCU.

The past work mainly focused on the function of proteins within signaling networks and to decipher the molecular lay-out of signaling networks. This has led to important and highly cited discoveries e.g. PKB/AKT downstream of PI3Kinase (together with Prof. Paul Coffer). Current work has expanded towards other signaling networks most importantly the involvement of metabolism in signaling and cell fate determination but also redox-signaling in collaboration with Dr Tobias Dansen.

Boudewijn is an elected member of EMBO and reviewer for the ERC, has been rewarded a VICI grant in 2002 and participates in the Dutch consortium on cancer research (CGC.nl).

• 2002: awarded VICI grant

1. Burgering, B. M, & Coffer, P. J. (1995). Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction. Nature, 376(6541), 599.

2. Essers, M. A., de Vries-Smits, L. M., Barker, N., Polderman, P. E., Burgering, B. M., & Korswagen, H. C. (2005). Functional interaction between ß-catenin and FOXO in oxidative stress signaling. Science, 308(5725), 1181-1184.

3. Kops, G. J., Dansen, T. B., Polderman, P. E., Saarloos, I., Wirtz, K. W., Coffer, P. J., ... & Burgering, B. M. (2002). Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress. Nature, 419(6904), 316.

4. Kops, G. J., de Ruiter, N. D., De Vries-Smits, A. M., Powell, D. R., Bos, J. L., & Burgering, B. M. (1999). Direct control of the Forkhead transcription factor AFX by protein kinase B. Nature, 398(6728), 630.
   ISO 690.

5. Medema, R. H., Kops, G. J., Bos, J. L., & Burgering, B. M. (2000). AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27 kip1. Nature, 404(6779), 782.

6. Rodríguez-Colman, M. J., Schewe, M., Meerlo, M., Stigter, E., Gerrits, J., Pras-Raves, M., ... & Verhoeven-Duif, N. (2017). Interplay between metabolic identities in the intestinal crypt supports stem cell function. Nature, 543(7645), 424.

7. Van der Horst, A., de Vries-Smits, A. M., Brenkman, A. B., van Triest, M. H., van den Broek, N., Colland, F., ... & Burgering, B. M. (2006). FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP. Nature cell biology, 8(10), 1064.