CRCStemCellDynamics SIGNED
Molecular Subtype Specific Stem Cell Dynamics in Developing and Established Colorectal Cancers
Total Cost €
0EC-Contrib. €
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Project "CRCStemCellDynamics" data sheet
The following table provides information about the project.
| Coordinator |
ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
Organization address contact info |
| Coordinator Country | Netherlands [NL] |
| Project website | http://tinyurl.com/vermeulenlab |
| Total cost | 1˙499˙875 € |
| EC max contribution | 1˙499˙875 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2014-STG |
| Funding Scheme | ERC-STG |
| Starting year | 2015 |
| Duration (year-month-day) | from 2015-04-01 to 2021-03-31 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM | NL (AMSTERDAM) | coordinator | 1˙499˙875.00 |
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Project objective
Annually 1.2 million new cases of colorectal cancer (CRC) are seen worldwide and over 50% of patients die of the disease making it a leading cause of cancer-related mortality. A crucial contributing factor to these disappointing figures is that CRC is a heterogeneous disease and tumours differ extensively in the clinical presentation and response to therapy. Recent unsupervised classification studies highlight that only a proportion of this heterogeneity can be explained by the variation in commonly found (epi-)genetic aberrations. Hence the origins of CRC heterogeneity remain poorly understood.
The central hypothesis of this research project is that the cell of origin contributes to the phenotype and functional properties of the pre-malignant clone and the resulting malignancy. To study this concept I will generate cell of origin- and mutation-specific molecular profiles of oncogenic clones and relate those to human CRC samples. Furthermore, I will quantitatively investigate how mutations and the cell of origin act in concert to determine the functional characteristics of the pre-malignant clone that ultimately develops into an invasive intestinal tumour. These studies are paralleled by the investigation of stem cell dynamics within established human CRCs by means of a novel marker independent lineage tracing strategy in combination with mathematical analysis techniques. This will provide critical and quantitative information on the relevance of the cancer stem cell concept in CRC and on the degree of inter-tumour variation with respect to the frequency and functional features of stem-like cells within individual CRCs and molecular subtypes of the disease. I am convinced that a better and quantitative understanding of the dynamical properties of stem cells during tumour development and within established CRCs will be pivotal for an improved classification, prevention and treatment of CRC.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2019 |
Kristiaan J. Lenos, Sophie C. Lodestijn, Scott K. Lyons, Maarten F. Bijlsma, Daniël M. Miedema, Louis Vermeulen A marker-independent lineage-tracing system to quantify clonal dynamics and stem cell functionality in cancer tissue published pages: 2648-2671, ISSN: 1754-2189, DOI: 10.1038/s41596-019-0194-y |
Nature Protocols 14/9 | 2019-10-10 |
| 2019 |
Maartje van der Heijden, Daniël M. Miedema, Bartlomiej Waclaw, Veronique L. Veenstra, Maria C. Lecca, Lisanne E. Nijman, Erik van Dijk, Sanne M. van Neerven, Sophie C. Lodestijn, Kristiaan J. Lenos, Nina E. de Groot, Pramudita R. Prasetyanti, Andrea Arricibita Varea, Douglas J. Winton, Jan Paul Medema, Edward Morrissey, Bauke Ylstra, Martin A. Nowak, Maarten F. Bijlsma, Louis Vermeulen Spatiotemporal regulation of clonogenicity in colorectal cancer xenografts published pages: 6140-6145, ISSN: 0027-8424, DOI: 10.1073/pnas.1813417116 |
Proceedings of the National Academy of Sciences 116/13 | 2019-10-10 |
| 2018 |
Kristiaan J. Lenos, Daniël M. Miedema, Sophie C. Lodestijn, Lisanne E. Nijman, Tom van den Bosch, Xavier Romero Ros, Filipe C. Lourenço, Maria C. Lecca, Maartje van der Heijden, Sanne M. van Neerven, Anita van Oort, Nicolas Leveille, Ronja S. Adam, Felipe de Sousa E Melo, Joy Otten, Patrick Veerman, Guillaume Hypolite, Lianne Koens, Scott K. Lyons, Giorgio Stassi, Douglas J. Winton, Jan Paul Med Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer published pages: 1193-1202, ISSN: 1465-7392, DOI: 10.1038/s41556-018-0179-z |
Nature Cell Biology 20/10 | 2019-10-10 |
| 2016 |
B L N Than, J F Linnekamp, T K Starr, D A Largaespada, A Rod, Y Zhang, V Bruner, J Abrahante, A Schumann, T Luczak, A Niemczyk, M G O\'Sullivan, J P Medema, R J A Fijneman, G A Meijer, E Van den Broek, C A Hodges, P M Scott, L Vermeulen and R T Cormier CFTR is a tumor suppressor gene in murine and human intestinal cancer published pages: , ISSN: 1476-5594, DOI: |
Oncogene | 2019-09-02 |
| 2016 |
Nicolas Léveillé, Louis Vermeulen Polycomb complex PRC1 as gatekeeper of intestinal stem cell identity published pages: 22-22, ISSN: 2306-9759, DOI: 10.21037/sci.2016.06.03 |
Stem Cell Investigation 3 | 2019-09-02 |
| 2016 |
Felipe de Sousa e Melo, Louis Vermeulen Wnt Signaling in Cancer Stem Cell Biology published pages: 60, ISSN: 2072-6694, DOI: 10.3390/cancers8070060 |
Cancers 8/7 | 2019-09-02 |
| 2016 |
E Fessler, M Jansen, F De Sousa E Melo, L Zhao, P R Prasetyanti, H Rodermond, R Kandimalla, J F Linnekamp, M Franitza, S R van Hooff, J H de Jong, S C Oppeneer, C J M van Noesel, E Dekker, G Stassi, X Wang, J P Medema and L Vermeulen A multidimensional network approach reveals microRNAs asdeterminants of the mesenchymal colorectal cancer subtype published pages: , ISSN: 1476-5594, DOI: |
Oncogene | 2019-09-02 |
| 2015 |
Justin Guinney,
Rodrigo Dienstmann,
Xin Wang,
Aurélien de Reyniès,
Andreas Schlicker,
Charlotte Soneson,
Laetitia Marisa,
Paul Roepman,
Gift Nyamundanda,
Paolo Angelino,
Brian M Bot,
Jeffrey S Morris,
Iris M Simon,
Sarah Gerster,
Evelyn Fessler,
Felipe De Sousa E Melo,
Edoardo Missiaglia,
Hena Ramay,
David Barras,
Krisztian Homicsko,
Dipen Maru,
Ganiraju C Manyam,
Bradley Broom,
Valerie Boige,
Beatriz Perez-Villamil,
Ted Laderas,
Ramon Salazar,
Joe W Gray,
Douglas Hanahan,
Josep Tabernero,
Rene Bernards,
Stephen H Friend,
Pierre Laurent-Puig,
Jan Paul Medema,
Anguraj Sadanandam,
Lodewyk Wessels,
Mauro Delorenzi,
Scott Kopetz,
Louis Vermeulen
& Sabine Tejpar The consensus molecular subtypes of colorectal cancer published pages: , ISSN: 1546-170X, DOI: |
Nature Medicine | 2019-09-02 |
| 2016 |
Maartje van der Heijden,
Cheryl D. Zimberlin,
Anna M. Nicholson,
Selcuk Colak,
Richard Kemp,
Sybren L. Meijer,
Jan Paul Medema,
Florian R. Greten,
Marnix Jansen,
Douglas J. Winton
& Louis Vermeulen Bcl-2 is a critical mediator of intestinal transformation published pages: , ISSN: 2041-1723, DOI: |
Nature Communications | 2019-09-02 |
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