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C O F F E R    LAB

center for molecular medicine × REGENERATIVE MEDICINE CENTER

 

Listening to cells to understand disease

WHILE a human cell contains around 20,000 genes, ONLY A HANDFUL OF THESE provide IT with a unique identity and will determine its FUNCTION AND fate. this relatively small number of genes can generate enormous biological complexity by being utilised in unique combinations and at specific levels. in the same way, only 88 keys on a piano are able to produce an almost infinite variety of music. the music produced will depend on both the combination of keys played and how hard they are pressed. In this way genes are able to control all aspects of cellular function, and it allows them to respond rapidly to changes in their environment. by listening to this 'cellular music' we hope to understand the molecular mechanisms underlying the pathogenesis of disease providing new therapeutic opportunities.

We are part of the center for molecular medicine and Located at the Regenerative Medicine Center, UMC Utrecht.

our research focuses on understanding the transcriptional control of cell fate decisions. this is placed in the context of stem cell biology, immunology and cancer. molecular and cell biological approaches are used in vitro and in vivo forming a 'translatable' research program with close connection to clinical collaborators.

Specific research questions that are currently being experimentally addressed include: 

1. UNderstanding transcriptional education of the mammary tumor niche

2. Understanding the regulation and function of autophagY in stem cells

3. Understanding the transcriptional control of neurogenesis

4. Targeting deregulated T cell metabolism in autoimmune disease

5. understanding EpigenEtic regulation of immune cells in health and disease

6. Therapeutic use of mesenchymal stem cell-derived exosomes

7. Characterizing the molecular effects of chromatin modifying drugs in hematopoiesis

 

Phone

+31 (0)30 212-1800

 

Location

Regenerative Medicine Center
Uppsalalaan 6
3584CT Utrecht

 

 

paul

Paul Coffer, PhD

Principle Investigator

Click here for bio

cornelieke

Cornelieke Pals

Lab Manager

koen

Koen Braat, PhD

SENIOR LECTURER/SCIENTIST

Project: disease modelling utilising induced pluripotent (iPS) cells

Program manager: UU Regenerative Medicine PhD program

jorg

Jorg van Loosdregt, PhD

Senior Scientist

Project: epigenetic regulation of autoimmune diseases

magdalena

Magdalena Lorenowicz, PhD

Senior scientist

Project: therapeutic application of stem cell-derived exosomes

enric

Enric Mocholi, PhD

Senior Postdoc

Project: (de)regulation of immunometabolism in autoimmune diseases

Guy

Guy Roukens, PhD

Senior Postdoc

Project: SOX4-mediated education of the mammary tumor niche

catalina

Catalina Gomez-Puerto

PhD Student

Project: transcriptional regulation of autophagy in stem cells

ana-rita
anita
desiree
luca
janneke
cindy
sandra
sanne

Ana Rita Lourenço

PhD Student

Project: transcriptional regulation of breast cancer metastasis

 

Anita Govers, MD

PHD STUDENT

Project: epigenetic regulation of hematopoeisis

 

Desiree Visser, MD

PhD Student

Project: genetic mechanisms underlying IBD

 

Luca Braciolli

PhD Student

Project: transcriptional control of neural stem cell function

 

Janneke Peeters

PhD Student (van Loosdregt/Coffer)

Project: epigentic regulation of autoimmune diseases

 

Cindy Frederiks

Technician

Project: understanding the role of SOX4 in breast cancer

 

Sandra Coenen

Technician (van loosdregt)

Project: function of autophagy in T cells

 

Sanne van Dooremalen

Technician (Lorenowicz)

Project: therapeutic application of stem cell-derived exosomes

Selected Publications

1.     Inhibition of super-enhancer activity in autoinflammatory site-derived T cells reduces disease-associated gene expression. Peeters, J.G., Vervoort, S.J., Tan, S.C., Mijnheer, G., de Roock, S., Vastert, S.J., Nieuwenhuis, E.E., van Wijk, F., Prakken, B.J., Creyghton, M.P., Coffer, P.J., Mokry, M. and van Loosdregt, J. (2015) Cell Rep. 12, 1986-96.

2.     van Loosdregt J, Coffer P.J. (2014) Post-translational modification networks regulating FOXP3 function. Trends Immunol. 35, 368-78.

3.     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

4.     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

5.     FOXP1 acts through a negative feedback loop to suppress FOXO-induced apoptosis. van Boxtel, R., Gomez-Puerto, C., Mokry, M., Eijkelboom, A., van der Vos, K.E., Nieuwenhuis, E.E.S., Burgering, B.M.T. and Coffer, P.J. (2013) Cell Death & Differentiation 20, 1219-1229

6.     The EGF-like growth factor Amphiregulin hampers effciient tumor therapy by enhacing regulatory T-cell function.Zaiss, D., van Loosdregt, J., Rjks, H., Gorlani, A., Bekker, C., Grone, A., Sibilia, M., van Bergen en Henegouwen, P., Roovers, R., Coffer, P.J. and Slijts, A.J. (2013) Immunity 38, 275-284

7.     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) Nat Cell Biol. 14,  829-37.

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

8.     Syntenin-mediated regulation of proteosomal degradation modulates SOX4 transcriptional output. Beekman, J.M., Vervoort, S., Dekkers, F., van Vessem, M.E., Vendelbosch, S., Brugalat-Panes, A., van Loosdregt, J., Braat, K. and Coffer, P.J. (2012) Oncogene 31, 2668-2679

9.     The role of SRY-related HMG box transcription factor 4 (SOX4) in tumorigenesis and metastasis: friend or foe? Vervoort, S., van Boxtel, R. and Coffer, P.J. (2012) Oncogene 32, 3397-3409

10.     Protein kinase B (PKB/c-akt) regulates homing of hematopoietic progenitors through modulation of their adhesive and migratory properties. Buitenhuis, M., van der Linden, E., Ulfman, L., Hofhuis, F., Bierings, M. and Coffer, P.J. (2010) Blood 116, 2373-2384

11.     Regulation of Treg functionality by acetylation-mediated Foxp3 protein stabilization. van Loosdregt, J., Vercoulen, Y, Guichelaar, T, van Gent, Y.J., Beekman, J.M., van Beekum, O., Brenkman, A., Hijnen, D., Mutis, T., Kalkhoven, E., Prakken, B.J. and Coffer, P.J. (2010) Blood 115, 965-974

12.     Tight control of MEK-ERK activation is essential in regulating proliferation, survival and cytokine production of CD34+ derived neutrophil progenitors. Geest, C.R., Buitenhuis, M., Groot-Koerkamp, M.J., Holstege, F.C., Vellenga, E.,Coffer, P.J. Blood 114, 3402-3412

13.     Protein kinase B (c-akt) regulates hematopoietic lineage choice decisions during myelopoiesis. Buitenhuis, M., Verhagen, L.P., van Deutekom, H.W., Castor, A., Verploegen, S., Koenderman, L., Jacobsen, S.E. and Coffer, P.J. (2007) Blood 111, 112-121

14.     Chronic protein Kinase B (PKB/c-akt) activation leads to apoptosis induced by ROS-mediated Foxo3a transcriptional upregulation. van Gorp, A.G.M., Pomeranz, K.M., Birkenkamp, K.U., Hui, R. C-Y., Lam, E. W-F. and Coffer, P.J. (2006) Cancer Res. 66, 10760-20769

15.     Forkhead-box transcription factors and there role in the immune system. Coffer, P.J. and Burgering, B.M.T. (2004) Nature Immunol. Rev. 4, 889-899

17.     FOXO3 can act as a critical effector of cell death induced by cytokine withdrawal: PKB enhanced cell survival through maintenance of mitochondrial integrity. Dijkers, P.F., Birkenkamp, K.U., Lam, E. W-F., Thomas, S.B., Lammers, J-W.J., Koenderman, L. and Coffer, P.J. (2002) J. Cell. Biol. 156, 531-542

18.     Expression of the pro-apoptotic Bcl-2 family member Bim is regulated by the Forkhead transcription factor FOXO3a. Dijkers, P.F., Medema, R.H., Lammers, J-W.J., Koenderman, L. and Coffer, P.J. (2000) Curr. Biol. 10, 1201-1204

19.     Cytokine-specific transcriptional regulation through an IL-5Ra-interacting protein. Geijsen, N., Uings, I., Pals, C., Armstrong, J., Raaijmakers, J.A.M., McKinnon, M., Lammers, J-W.J., Koenderman, L. and Coffer, P.J. (2001) Science 293, 1136-1138

20.     Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction. Burgering, B.M.Th. and Coffer, P.J. (1995) Nature 376, 599-602

see also News & Views: Downward, 1995. Nature 376, 553-554.

 

Contact Us

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

 
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