Derk (D.) Amsen PhD
Immunology, Molecular Biology and Mouse Genetics
The ability of T cells to recognize transplantation antigens constitutes a hurdle in all cellular transplantation processes, including transplantation of blood. On the other hand, harnessing this property also provides opportunities, for instance in stem cell therapy of leukemia patients, where T cells included in the graft destroy residual tumor cells. As the immune system primarily evolved to protect us from microbial invasion, we make use of microbial infection models to unravel the molecular pathways governing the functions of both CD4 and CD8 T cells. We employ the genetic power of mouse models to acquire fundamental insights into such questions as: how do T cells differentiate into effector cells that control the generation of antibodies? How are potent cytolytic T cells generated? What is the molecular basis for the development of immunological memory? We aim to translate such fundamental insights for the improvement of human therapies involving T cell transplantation.
- Viral infection models
- In vivo monitoring and manipulation of immune responses
- Retroviral and Lentiviral expression systems
- Mouse transgenesis
|2013-present||Group Leader at Sanquin Research, Amsterdam|
|2006-2012||Group Leader at the Department of Cell Biology, AMC Amsterdam|
|2004-2006||Associate research Scientist, Section of Immunobiology, Yale University (Chief: Richard Flavell)|
|1998-2004||Postdoctoral Associate, Section of Immunobiology, Yale University (Chief: Richard Flavell)|
|1993-1998||PhD, Department of Immunobiology, Netherlands Cancer Institute|
Backer RA, Helbig C, Gentek R, Kent A, Laidlaw BJ, Dominguez CX, de Souza YS, van Trierum SE, van Beek R, Rimmelzwaan GF, ten Brinke A, Willemsen AM, van Kampen AH, Kaech SM, Blander JM, van Gisbergen K, Amsen D. A central role for Notch in effector CD8+ T cell differentiation. Nat Immunol 2014; Oct 26. [Epub ahead of print]
Nair-Gupta P, Baccarini A, Tung N, Seyffer F, Florey O, Huang Y, Banerjee M, Overholtzer M, Roche PA, Tampé R, Brown BD, Amsen D, Whiteheart SW, Blander JM. TLR Signals Induce Phagosomal MHC-I Delivery from the Endosomal Recycling Compartment to Allow Crosspresentation. Cell 2014; 158(3):506-21.
Gentek R, Munneke JM, Helbig C, Blom B, Hazenberg MD, Spits H. Amsen, D. Modulation of signal strength switches Notch from an inducer of T cells to an inducer of ILC2. Front Immunol 2013; 4:334.
Amsen D, Backer RA, Helbig, C. Decisions on the road to memory. Adv Exp Med Biol 2013; 785:107-20.
Karrich JJ, Balzarolo M, Schmidlin H, Libouban M, Nagasawa M, Gentek R, Kamihira S, Maeda T, Amsen D, Wolkers MC and Blom B. The transcription factor Spi-B regulates human plasmacytoid dendritic cell survival through direct induction of the anti-apoptotic gene BCL2-A1. Blood 2012; 119(22):5191-200.
Helbig C, Gentek R, Backer RA, de Souza YS, Derks IAM, Eldering E, Wagner K, Jankovic D, Gridley T, Moerland P, Flavell RA and Amsen D. Notch controls the magnitude of CD4+ T cell responses by promoting cellular longevity. Proc Natl Acad Sci U.S.A. 2012; 109(23):9041-6.
Nair P, Amsen D and Blander JM. Co-ordination of Incoming and Outgoing Traffic in Antigen-Presenting Cells by Pattern Recognition Receptors and T Cells. Traffic 2011; 12(12):1669-76. (equal contribution senior author)
Sander LE, Davis MJ, Boekschoten MV, Amsen D, Dascher CC, Ryffel B, Swanson JA, Müller M and Blander JM. Detection of prokaryotic mRNA signifies microbial viability and promotes immunity. Nature 2011; 474(7351):385-9.
Blander JM and Amsen D. Amino acid addiction. Science 2009; 324(5932):1282-3. (perspective)
Amsen D, Splilianakis C and Flavell RA. How are TH1- and TH2-effector cells made? Current Opinion in Immunology 2009; 21(2):153-60.
Amsen D, Antov A and Flavell RA. The different faces of Notch in T-helper-cell differentiation. Nature Reviews in Immunology 2009; 9(2):116-24. (Corresponding author)
Amsen D, De Visser K, Town T. Approaches to determine expression of inflammatory cytokines. Methods in Molecular Medicine 2009; 511:107-42. (Corrresponding author)
Amsen D Antov AN, Jankovic D, Sher FA, Radtke F, Souabni A, Busslinger M, McCright B, Gridley T and Flavell RA Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch. Immunity 2007; 27(1):89-99. (Corresponding author)
Amsen D, Blander JM, Lee GR, Tanigaki K, Honjo T and Flavell RA. Instruction of Distinct CD4 T helper Cell Fates By Different Notch Ligands on Antigen Presenting Cells. Cell 2004; 117(4):515-26.
Amsen D, Kruisbeek AM, Bos JL and Reedquist KA. Activation of the Ras related GTPase Rap1 by thymocyte TCR engagement and during selection. European Journal of Immunology 2000; 30(10):2832-41.
Amsen D, Revilla Calvo C, Osborne BA and Kruisbeek A M. Costimulatory signals are required for induction of Nur77 during negative selection of CD4+CD8+ thymocytes. Proc Natl Acad Sci U.S.A. 1999; 96(2):622-7.
Amsen D and Kruisbeek AM. Thymocyte selection: not by TCR alone. Immunological Reviews 1998; 165:209-29.
Gravestein LA, Amsen D, Boes M, Revilla Calvo C, Kruisbeek AM and Borst J. The Tumor Necrosis Factor receptor family member CD27 signals to Jun N-terminal kinase via Traf-2. European Journal of Immunology 1998; 28(7):2208-16.
Revilla Calvo C, Amsen D and Kruisbeek AM. Cytotoxic T lymphocyte antigen 4 (CTLA4) interferes with extracellular signal-regulated kinase (ERK) and Jun NH2-terminal kinase (JNK) activation, but does not affect phosphorylation of T cell receptor and ZAP70. Journal of Experimental Medicine 1997; 186(10):1645-53. (shared first authorship)
Amsen D and Kruisbeek AM. CD28-B7 interactions function to co-stimulate clonal deletion of double positive thymocytes. International Immunology 1996; 8(12):1927-36.
Kruisbeek AM and Amsen D. Mechanisms underlying T cell tolerance. Current Opinion in Immunology 1996; 8(2):233-44.
Bain G, Robanus Maandag E, Izon DJ, Amsen D, Kruisbeek AM, Weintraub BC, Krop I, Schlissel MS, Feeney AJ, Van Roon M, Van der Valk M, Te Riele HPJ, Berns A and Murre C. E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements. Cell 1994; 79(5):885-92.