Paul Coffer

Principle Investigator

paul_lab1

Biographical sketch

Paul Coffer studied Biochemistry at Oxford University and obtained his PhD from the Ludwig Institute for Cancer Research in London, UK. Here, in the lab of Prof. James Woodgett, he identified Protein Kinase B (PKB/c-akt), which was at that time a novel player in intracellular signal transduction.

He subsequently relocated to the Hubrecht Institute for Developmental Biology and Stem Cell Research in Utrecht, The Netherlands. This postdoctoral research was involved in investigating the mechanisms by which hematopoietic cytokines can regulate gene expression through transcription factor phosphorylation. Furthermore, at this time, together with Prof. Boudewijn Burgering (Molecular Cancer Research, University Medical Center Utrecht), he also demonstrated that PKB/c-akt was a central mediator of growth factor and cytokine signaling pathways.

Paul then moved to the Department of Respiratory Medicine at the University Medical Centre Utrecht to initiate his own research group. During this period, work focused on studying the role of intracellular signal transduction pathways in regulating both the production and function of leukocytes. A particular focus of this research was in determining signal specificity between hematopoietic cytokines. Work in his group also demonstrated that PKB-mediated phosphorylation of Forkhead transcription factors (FOXO) was critical for the regulation of leukocyte proliferation and survival. These studies laid the groundwork for his further research into the regulation of hematopoietic cell-fate decisions.

In 2005 Paul Coffer was appointed Professor of Pediatric Immunology at the University Medical Centre Utrecht and moved to the Wilhelmina Children’s Hospital where he works within the Department of Immunology and the Center for Molecular and Cellular Intervention (CMCI).

In 2011 he moved to the Department of Cell Biology at the University Medical Center Utrecht where he was appointed Professor of Stem Cell Biology. Here he is continuing his research into the regulation of intracellular signalling pathways and their role in regulating stem cell fate decisions. Current work in his research group is focused on applying this fundamental research to the study of cancer, immunology and regenerative medicine.

Key Publications

Modulation of glutamine metabolism by the PI(3)K-PKB-FOXO network regulates autophagy.
van der Vos KE, Eliasson P, Proikas-Cezanne T, Vervoort SJ, van Boxtel R, Putker M, van Zutphen IJ, Mauthe M, Zellmer S, Pals C, Verhagen LP, Groot-Koerkamp MJ, Braat AK, Dansen TB, Holstege FC, Gebhardt R, Burgering BM, Coffer PJ. (2012) Nat Cell Biol. 14:829-37.

Syntenin-mediated regulation of Sox4 proteasomal degradation modulates transcriptional output.
Beekman JM, Vervoort SJ, Dekkers F, van Vessem ME, Vendelbosch S,Brugulat-Panès A, van Loosdregt J, Braat AK, Coffer PJ. (2012) Oncogene 31:2668-79.

Regulation of Treg functionality by acetylation-mediated FOXP3 protein stabilization.
van Loosdregt, J., Vercoulen, Y., Guichelaar, T., van Gent, Y.J., Beekman, J., Brenkman, A, Hijnen, D., Mutis, T., Kalkhoven, E., Prakken, B.J. and Coffer, P.J. (2011)
Blood 115, 965-974

Regulation of myelopoiesis through syntenin-mediated modulation of IL-5 receptor output.
Beekman, J.M., Verhagen, L.P., Geijsen, N. and Coffer, P.J. (2009)
Blood 114, 3917-3927

Tight control of MEK-ERK activation is essential in regulating proliferation, survival and cytokine prodiction of CD34 derived neutrophil progenitors.
Geest, C.R., Buitenhuis, M. Groot-Koerkamp, M.J., Holstege, F.C., Vellenga, E. and Coffer, P.J. (2009)
Blood 114, 3402-3412

Protein kinase B (c-akt) regulates hematopoietic lineage 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

Chronic protein kinase B (c-akt) activation leads to apoptosis induced by ROS-mediated Foxo3a transcriptional regulation.
van Gorp, A.G.M., Pomeranz, K.M., Birkenkamp, K., Hui, K.U., Lam, E.W-F. and Coffer, P.J. (2007)
Cancer Res. 66, 10760-20769

FOXO3a can act as a critical effector of cell death induced by cytokine withdrawal: PKB enchanced cell survival through maintenance of mitochondrial integrity.
Dijkers PF, Birkenkamp KU, Lam EWF, Thomas SB, Lammers JWJ, Koenderman L and Coffer PJ. 2002
J. Cell. Biol. 156, 531-542 

Cytokine-specific transcriptional regulation through an IL-5Ralfa-interacting protein.
Geijsen N, Uings I, Pals C, Armstrong J, Raaijmakers JAM, McKinnon M, Lammers JWJ, Koenderman L and Coffer PJ. 2001
Science 293, 1136-1138 

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

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

Reviews

van der Vos KE, Coffer PJ. Glutamine metabolism links growth factor signaling to the regulation of autophagy. Autophagy. 2012 Sep 20;8(12).

van der Vos KE, Gomez-Puerto C, Coffer PJ. Regulation of autophagy by Forkhead box (FOX) O transcription factors. Adv Enzyme Regul. 2011 Nov 10. [Epub ahead of print]

van der Vos KE, Coffer PJ. The extending network of FOXO transcriptional target genes. Antioxid Redox Signal. 2011 Feb 15;14(4):579-92.

The role of the PI3K-PKB signalling module in the regulation of hematopoieis. Buitenhuis, M. and Coffer, P.J. (2009) Cell Cycle 8, 560-566

The ins-and-outs of syntenin, a multifunctional adapter protein. Beekman, J. and Coffer, P.J. (2008) J. Cell Sci. 121, 1349-1355

FOXO binding partners: it takes two-to tango. van der Vos, K.A. and Coffer, P.J. (2008) Oncogene 27, 2289-2299

Stressed in the marrow: FoxOs stem tumour growth. (2007) Coffer, P.J. and Burgering, B.M.T. Nature Cell Biol. 9, 251-253

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

Transcriptional regulation of lymphocyte quiescence: as cunning as a FOX. Coffer, P.J. (2003) Trends Immunol. 24, 470-471

FOXO transcription factors as regulators of immune homeostasis: molecules to die for? Birkenkamp, K.U. and Coffer, P.J. (2003) J. Immunol. 171, 1623-1629

Specificity in cytokine signal transduction: lessons learned from the IL-3/IL-5/GM-CSF receptor family. Geijsen, N., Koenderman, L. and Coffer, P.J. (2001) Cytokine & Growth Factor Reviews 12, 19-25

Protein Kinase B (c-akt): a multifunctional mediator of PI-3K activation. Coffer, P.J., Jin, J. and Woodgett, J.R. (1998) Biochem. J. 335, 1-35

See publication page for a full list of published articles and reviews


Grants obtained

Dutch Asthma Foundation (NAF)
Development and characterisation of disease monitors for COPD
Coffer, P.J. and Koenderman, L.

Dutch Asthma Foundation (NAF)
Characterisation and antagonism of cytokine-priming of human granulocytes
Coffer, P.J. and Koenderman, L.

Netherlands Cancer Society (NKB)
Cytokine-specific signalling regulating myeloid cell survival, proliferation and differentiation
Coffer, P.J.

Netherlands Scientific Organisation (NWO)
PI-3 kinase/protein kinase B signalling: regulation and function
Coffer, P.J., Medema, R. and Burgering, B.M.T.

Netherlands Scientific Organisation (NWO; VIDI)
Divide, differentiate or die? Moelcular mechanisms regulating hematopoietic cell fate decisions
Coffer, P.J.

Netherlands Cancer Society (NKB)
Characterisation of signalling defects in granulocytes/myeloid precursors from MDS patients
Coffer, P.J. and Vellenga, E.

Netherlands Cancer Society (NKB)
Dysfunction of hematopoietic stem cells in pediatric leukemia
Coffer, P.J.

Landsteiner Organisation for Blood Transfusion (LSBR)
Inhibitory immune receptors as regulators of hematopoiesis
Coffer, P.J. and Meyaard, L.

Wilhelmina Children's Hospital Foundation (WKZ Fonds)
HDAC inhibitors and hematopoiesis: towards novel therapies for pediatric MDS
Coffer, P.J. and Bierings, M.

Dutch Rheumatology Foundation (RheumaFonds)
Understanding FOXP3: towards development of novel therapeutic strategies for JIA
Coffer, P.J.

Center for Translational Molecular Medicine (CTMM)
Development of an OncoKinase chip for leukemia
Coffer, P.J., van Helfoort, J. and Burgering, B.M.T.

European Research Projects on Rare Diseases (ERARE)
Development and characterization of iPS cell lines for studying severe congential neutropenia
Coffer, P.J.

Netherlands Institute for Regenerative Medicine (NIRM)
Molecular and cellular characterization of mesenchymal stem cell populations
Coffer, P.J.

Netherlands Cancer Society (NKB)
Role of autophagy in regulation of hematopoiesis
Coffer, P.J., Schuringa, J.J. and Vellenga, E.
http://www.ncbi.nlm.nih.gov/pubmed/21986941
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