Listening to cells to understand disease
WHILE every human cell contains around 20,000 genes, ONLY A HANDFUL OF THESE actually provide IT with a unique identity. this relatively small number of genes can generate enormous biological complexity by being utilised in unique combinations, at specific times and at precise levels. in the same way, while there are only 88 keys on a piano, playing these keys can generate an almost infinite variety of music. the music produced will depend on both the combination of keys played and how long and hard they are pressed. In this way, combinations of genes are able to control all aspects of biological function. by listening to this cellular 'music' we hope to understand the molecular mechanisms underlying the pathogenesis of disease, leading to new therapeutic opportunities.
our research IS driven by both fundamental and clinical questions in the fields of cancer, immunology and stem cells. examples of research areas that are currently being explored include:
- UNderstanding and manipulating INTERACTIONS BETWEEN IMMUNE CELLS & TUMORS
- transcriptional control of epithelial plasticity and metastasis
- Targeting deregulated T cell metabolism in autoimmune disease
- Therapeutic use of mesenchymal stem cell-derived exosomES
BIOLOGICAL PROCESSES WE ARE INTERESTED IN INCLUDE: anergy, gene TRANSCRIPTION, intracellular SIGNALING, EPIGENETIC regulation, cellular METABOLISM, AUTOPHAGY & METASTASIS.
Our research uses a broad range of molecular and cell biological approaches, as well as in vivo and ex-vivo models of disease. This forms a 'translatable' research program with close connection with our clinical collaborators.
We are part of the center for molecular medicine and Located at the Regenerative Medicine Center, UMC Utrecht.
+31 (0)30 212-1800
Regenerative Medicine Center
Chair, Utrecht University Regenerative Medicine PhD program
Manager of Research, Division LAB, UMC Utrecht
Program Manager, Utrecht University Regenerative Medicine PhD program
Interest: therapeutic application of stem cell-derived exosomes
Interest: the mammary tumor niche
Interest: (de)regulation of immunometabolism in autoimmune diseases
Interest: (de)regulation of immunometabolism in pediatric arthristis
Interest: anergy and autophagy in T cell activation
Interest: understanding the role of SOX4 in breast cancer
PhD student (supervisor Prof. Marc Timmers)
Interest: TFIID assembly and function
Representative publications for current research themes:
1. Nemo-like kinase drives Foxp3 stability and is critical for maintenance of immune tolerance by regulatory T cells. Fleskens, V., Minutti, C., Wu, X., Wei, P., Pals, C.E.G.M., McCrae, J., Hemmers, S., Groenewold, V., Rudensky, A., Pan, F., Li, H., Zaiss, D. and Coffer, P.J. Cell Reports, in press.
2. Forkhead transcription factors as context-dependent regulators of lymphocyte homeostasis. Zaiss, D. and Coffer, P.J. (2018) Nature Reviews Immunology 18, 703-715.
3. SOX4-SMAD3 interaction redirects TGF-β-mediated transcriptional output in a context-dependent manner. Vervoort, S.J., Lourenco, A.R., Tufegdzic-Vidakovic, A., Sandoval, J.L., Rueda, O.M., Frederiks, C., Russell, R., Caldas, C., Bruna, A. and Coffer, P.J. (2018) Nucleic Acid Research 46, 9578-9590.
4. Autophagy is a tolerance-avoidance mechanism that modulates TCR-mediated signaling and cell metabolism to prevent the induction of T cell anergy. Mocholi, E., Dowling, S.D., Botbol, Y., Gruber, R.C., Ray, A.K., Vastert, S., Shafit-Zagardo, B., Coffer, P.J. and Macian, F. (2018) Cell Reports 24, 1136-1150.
5. Global transcriptional analysis identifies a novel role for SOX4 in tumor-induced angiogenesis. Vervoort, S.J., de Jong, O.G., Vermeulen, J.F., Bella, L., Lourenco, A-R., Frederiks, C., Tufegdzic-Vidakovic, A., Russell, R., Moelans,C., van Amersfoort, M., Dallman, M.J., Bruna, A., Caldas, C., Nieuwenhuis, E., van der Wall, E., Derksen, P., van Diest, P., Lam, W. W-F., Verhaar, M., Mokry, M. and Coffer, P.J. eLife, Dec 3;7.
6. Bartels M, Govers AM, Fleskens V, Lourenço AR, Pals CE, Vervoort SJ, van Gent R, Brenkman AB, Bierings MB, Ackerman SJ, van Loosdregt J, Coffer PJ. (2015) Acetylation of C/EBPε is a prerequisite for terminal neutrophil differentiation. Blood. 125, 1782-92
7. Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, Liu H, Cross JR, Pfeffer K, Coffer PJ, Rudensky AY. (2013) Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504, 451-5
8. USP7/HAUSP-mediated stabilization of Foxp3 increases Treg suppressive capacity. van Loosdregt, J., Fleskens, V., Fu, J., Brenkman, A.J., Bekker, C.P.J., Pals, C.E.G.M., Meerding, J., Berkers, C.R., Barbi, J., Grone, A., Sijts, A.J.M., Maurice, M.M., Kalkhoven, E., Prakken, B.J., Ovaa, O., Pan, F., Zaiss, D.M.W. and Coffer, P.J. (2013) Immunity 39, 259-271
9. Canonical Wnt signaling negatively modulates T regulatory cell function. van Loosdregt, J., Fleskens, V., Tiemessen, M.T., Mokry, M., van Boxtel, R., Meerding, J., Pals, C.E.G.M., Kurek, D., Baert, M.R., Delmarre, E.M., Grone, A., Groot-Koerkamp, M.J., Sijts, A.A.M., Maurice, M.M., van Es, J.H., ten Berge, D., Holstege, F.C., Staal, F.J.T., Zaiss, D.M.W., Prakken, B.J. and Coffer, P.J. (2013) Immunity 39, 298-310
10. Modulation of glutamine metabolism by the PI(3)K-PKB-FOXO network regulates autophagy. van der Vos, K.E., Eliasson, P., Proikas-Cezanne, T., Vervoort, S.J., van Boxtel, R., Putker M., van Zutphen, I.J., Mauthe, M., Zellmer, S., Pals, C., Verhagen, L.P., Groot-Koerkamp, M.J., Braat, A.K., Dansen, T.B., Holstege, F.C., Gebhardt, R., Burgering, B.M., Coffer, P.J. (2012) Nature Cell Biology 14, 829-37