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c o f f e r l a b

center for molecular medicine × REGENERATIVE MEDICINE CENTER

 

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.

 

Phone

+31 (0)30 212-1800

 

Location

Regenerative Medicine Center
Uppsalalaan 8
3584CT Utrecht

 

 

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Paul Coffer

Group Leader

Chair, Utrecht University Regenerative Medicine PhD program

Manager of Research, Division LAB, UMC Utrecht

Cornelieke

Cornelieke Pals

Lab Manager

Koen

Koen Braat

Senior Lecturer

Program Manager, Utrecht University Regenerative Medicine PhD program

Magdalena

Magdalena Lorenowicz

Senior Scientist

Interest: therapeutic application of stem cell-derived exosomes

Guy

Guy Roukens

Senior Postdoc

Interest: the mammary tumor niche

Enric

Enric Mocholi

Senior Postdoc

Interest: (de)regulation of immunometabolism in autoimmune diseases

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Laura Russo

RESEARCH ASSOCIATE

Interest: (de)regulation of immunometabolism in pediatric arthristis

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Alessandro Cutilli

PhD Student

Interest: anergy and autophagy in T cell activation

Cindy

Cindy Frederiks

Technician

Interest: understanding the role of SOX4 in breast cancer

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Simona Antonova

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

          see also News & Views: Gombart, 2015. Blood 125,1688-90

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 

          see also News & Views: Laurence et al, 2013. Immunity 39, 201-203

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

          see also News & Views: Sandri, 2012. Nature Cell Biology 4, 786-788


Click here for a full list of publications

Contact Us

Regenerative Medicine Center, UMC Utrecht, Uppsalalaan 6, 3584CT Utrecht, The Netherlands

 
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