MOLECULAR IMMUNOLOGY LAB (MIL)
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@ Paul Coffer
The regulation of immune homeostasis requires precise communication between cells of the innate and adaptive immune system. Dysregulation in the production or function of components of both types of cellular immunity can lead to a variety of pathological disorders ranging from autoimmune diseases and inflammation to leukemia and immune deficiencies. One of our longstanding research questions is to identify the specific molecular mechanisms regulating the production and function of cells of the immune system.
Our research is focused in three major programs:
1. Immunology Program
2. Hematooncology Program
3. Regenerative Medicine ProgramWhile primarily fundamental bench-based research, through collaborative ventures with scientists and clinicians within the University Medical Center research, work is directed towards the following goals:
- understanding the molecular basis of childhood diseases
- improving gene, stem cell and cellular therapies
- development of novel therapies for childhood diseases- Cornelieke Pals (Head Technician)
- Koen Braat (Head stem cell research program)
- Jeffrey Beekman (Principle Invesigator)
- Pernilla Eliasson (Postdoc)
- Ruben van Boxtel (Postdoc)
- Marije Bartels (MD PhD student)
- Stephin Vervoort (PhD student)
- Jorg van Loosdregt (PhD student)
- Tessa Steevels (PhD student)
- Marit van Meegan (MD PhD student)
- Veerle Flesken (PhD student)
- Florijn Dekkers (PhD student)
- Liesbeth Verhagen, (Technician)
- Estel Slump (Technician)
- Lodewijk Vijftigschild (Technician)
- Cornelis Bekker (Technician)
- Evelien Kruisselbrink (Technician)
Protein kinase B (c-akt) regulates homing of hematopoietic progenitors through modulation of their adhesive and migratory properties. Buitenhuis, M., van de Linden, E., Ulfman, L., Hofhuis, F., Bierings, M. and Coffer, P.J. (2010)
Blood, in press
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. (2010)
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
p38 MAP kinase inhibits neutrophil development through phosphorylation of C/EBPalpha on serine 21. Geest, C.R., Buitenhuis, M., Laarhove, A.G., Bierings, M.B., Bruin, M.C.A., Velenga, E. and Coffer, P.J. (2009)
Stem Cells 27, 2271-2282
HMG-CoA reductase inhibition induces IL-1beta release through Rac1/PI3K/PKB-dependent caspase-1 activation. Kuijk, L.M., Beekman, J.M., Waterham, H.R>, Frenkel, J. and Coffer, P.J. (2008)
Blood 112, 3563-3573
Stressed marrow: FoxOs stem tumor growth.Coffer, P.J. and Burgering, B.M.T.
Nature Cell Biol. 9, 251-253
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
Molecular mechanisms underlying F1P1L1-PDGFRA mediated myeloproliferation.Buitenhuis, M., Verhagen, L.P., Cools, J. and Coffer, P.J. (2007)
Cancer Res. 67, 3759-3766
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
Forhead-box transcription factors and their role in the immune system.Coffer, P.J. and Burgering, B.M.T. (2005)
Nature Immunol. Rev. 4, 1-12
Characterization of the role of CaMKI Like Kinase (CKLiK) in human granulocyte function.Verploegen, S., Ulfman, L., van Deutekom, H., van Aalst, C., Honing, H., Lammers, J-W.J., Koenderman, L. and Coffer, P.J. (2005).
Blood 106, 1076-1083
Differential regulation of granulopoiesis by the basic Helis Loop Helis transcriptional inhibitors Id1 and Id2.Buitenhuis B, van Deutekom HWM, Verhagen LP, Castor H, Jacobsen SE, Lammers JWJ, Koenderman L and Coffer PJ. 2005
Blood 105, 4272-4281
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
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
Netherlands Institute for Regenerative Medicine (NIRM)
Molecular and cellular characterization of mesenchymal stem cell populations