foto

Dr. K. Weijer PhD

Position
Other
Main activities
Research
Specialisation
Development and improvement of humanized (HIS) mice as in vivo model for man.
Focus of research

To study human T cell differentiation and development, a Hu-SCID mouse model was set up. RAG2-/-/gc-/- double KO mice, which have no T, B and NK cells, are used as immunodeficient mice, in which human fetal hematopoietic stem cells or tissues (from fetal thymus, liver, spleen, bone, cord blood or mobilized peripheral blood cells), are transplanted. Stem cells or precursor cells can be transduced with a gene of interest. Subsequently, the fate of the injected cells can be followed in the HIS-mouse (human immune system mouse) and the role of the gene can be studied.
Since substantial numbers of human cells are present this HIS-mouse can be used to test vaccines and drugs.
 

Key publications
  • Legrand N, Weijer K, Spits H, Experimental model for the study of the human immune system: production and monitoring of "human immune system" Rag2-/-gamma c-/- mice. METHODS MOL BIOL 2008;415:65-82 [PubMed]
  • Legrand N, Cupedo T, van Lent AU, Ebeli MJ, Weijer K, Hanke T, Spits H, Transient accumulation of human mature thymocytes and regulatory T cells with CD28 superagonist in "human immune system" Rag2(-/-)gammac(-/-) mice. BLOOD 2006;108 (1):238-245 [PubMed]
  • Legrand N, Weijer K, Spits H, Experimental models to study development and function of the human immune system in vivo. J IMMUNOL 2006;176 (4):2053-2058 [PubMed]
  • Gimeno R, Weijer K, Voordouw A, Uittenbogaart CH, Legrand N, Alves NL, Wijnands E, Blom B, Spits H, Monitoring the effect of gene silencing by RNA interference in human CD34+ cells injected into newborn RAG2-/- gammac-/- mice: functional inactivation of p53 in developing T cells. BLOOD 2004;104 (13):3886-3893 [PubMed]
  • Weijer K, Uittenbogaart CH, Voordouw A, Couwenberg F, Seppen J, Blom B, Vyth-Dreese FA, Spits H, Intrathymic and extrathymic development of human plasmacytoid dendritic cell precursors in vivo. BLOOD 2002;99 (8):2752-2759 [PubMed]
All Publications
Curriculum Vitae


Academisch Medisch Centrum AMC
Universiteit van Amsterdam
Afdeling Celbiologie Histologie
 

RESEARCH STAFF MEMBER

K. Weijer

 

Affiliation:

Kees Weijer DVM PhD
University of Amsterdam
Academisch Medisch Centrum
Department of Cellbiology and Histology
Room L3-117
Meibergdreef 15
1105 AZ Amsterdam
tel. *31.20.566.6256
fax.*31.20.697.4156



Research specialities:

To study human T cell differentiation and development, a Hu-SCID mouse model was set up. RAG2-/-/gc-/- double KO mice, which have no T, B and NK cells, are used as immunodeficient mice, in which human fetal hematopoietic stem cells or tissues (from fetal thymus, liver, spleen, bone, cord blood or mobilized peripheral blood cells), are transplanted. Hemapoietic stem cells or precursor cells can be transduced with a gene of interest. Subsequently, the fate of the injected cells can be followed in the HIS-mouse (human immune system mouse) and the role of the gene can be studied.
Since substantial numbers of human cells are present this HIS-mouse can be used to test candidate vaccines, antibodies and other biologicals.
 

Key publications:

Res P., Blom B., Hori T., Weijer K., Spits H. 1997. Downregulation of CD1 marks acquisition of functional maturation of human thymocytes and defines a control point in late stages of human T cell development. J. Exp. Med., 185:141-152.

Blom B., Res .P, Noteboom E., Weijer K., Spits H. 1997. Prethymic CD34+ progenitors capable of developing into T cells are not committed to the T cell lineage. J. Immunol.;158:3571 3577.

Jaleco AC., Blom B., Res P., Weijer K., Lanier LL.., Phillips JH., Spits H. 1997. Fetal liver contains committed NK progenitors, but is not a site for development of CD34+ cells into T cells. J Immunol., 159:694 702.

Heemskerk MHM., Blom B., Nolan G., Stegmann APA., Bakker AQ., Weijer K., Res PCM., Spits H. 1997. Inhibition of T cell and promotion of Natural Killer Cell Development by the Dominant Negative Helix Loop Helix Factor Id3. J. Exp. Med., 186:1597-1602.

Jaleco AC., Stegmann AP., Heemskerk MH., Couwenberg F., Bakker AQ., Weijer K., Spits H. 1999. Genetic modification of human B-cell development: B-cell development is inhibited by the dominant negative helix loop helix factor Id3. Blood, 94:2637-2646.

Weijer K., Uittenbogaart CH., Voordouw A., Couwenberg F., Seppen J., Blom B., Vyth-Dreese F., Spits H. 2002. Intrathymic and extrathymic development of human plasmacytoid dendritic cell precursors in vivo. Blood, 99: 2752-2759.

van Rijn RS, Simonetti ER, Hagenbeek A, Hogenes MC, de Weger RA, Canninga-van Dijk MR, Weijer K, Spits H, Storm G, van Bloois L, Rijkers G, Martens AC, Ebeling SB 2003. A new xenograft model for graft-versus-host disease by intravenous transfer of human peripheral blood mononuclear cells in RAG2-/- gammac-/- double-mutant mice. Blood. 102:2522-31.

Schotte R, Rissoan MC, Bendriss-Vermare N, Bridon JM, Duhen T, Weijer K, Briere F, Spits H 2003. The transcription factor Spi-B is expressed in plasmacytoid DC precursors and inhibits T-, B-, and NK-cell development. Blood 101:1015-23.

Verra NC, Jorritsma A, Weijer K, Ruizendaal JJ, Voordouw A, Weder P, Hooijberg E, Schumacher TN, Haanen JB, Spits H, Luiten RM 2004. Human Telomerase Reverse Transcriptase-Transduced Human Cytotoxic T Cells Suppress the Growth of Human Melanoma in Immunodeficient mice. Cancer Res. 64: 2153-2161.
 


Ramon Gimeno, Kees Weijer, Arie Voordouw, Christel H. Uittenbogaart, Nicolas Legrand, Nuno L. Alves, Erwin Wijnands, Bianca Blom, and Hergen Spits 2004. Monitoring the effect of gene silencing by RNA interference in human CD34+ cells injected into newborn RAG2-/- c-/- mice: functional inactivation of p53 in developing T cells. Blood 104: 3886 - 3893.

Remko Schotte, Maho Nagasawa, Kees Weijer, Hergen Spits, and Bianca Blom 2004. The ETS Transcription Factor Spi-B Is Required for Human Plasmacytoid Dendritic Cell Development. J. Exp. Med. 200: 1503 - 1509.

Tom Cupedo, Maho Nagasawa, Kees Weijer, Bianca Blom, Hergen Spits 2005. Development and activation of regulatory T cells in the human fetus. Eur.J.Immunol. 35:383-390

Legrand N, Cupedo T, van Lent AU, Ebeli MJ, Weijer K, Hanke T, Spits H 2006. Transient accumulation of human mature thymocytes and regulatory T cells with CD28 super agonist in "human immune system" Rag2(-/-)gamma c(-/-) mice. Blood 108(1):238-245

Legrand N, Weijer K, Spits H. 2006. Experimental models to study development and function of the human immune system in vivo. J Immunology 176(4):2053-2058


Deurholt T, ten Bloemendaal L, Chatta AA, van Wijk AC, Weijer K, Seppen J, Elferink RP, Chamuleau RA, Hoekstra R 2006. In vitro functionality of human fetal liver cells and clonal derivatives under proliferative conditions. Cell Transplant 15(8-9):811-22.


Dong Sung An, Betty Poon, Raphaël Ho Tsong Fang, Kees Weijer, Bianca Blom, Hergen Spits, Irvin S. Y. Chen and Christel Uittenbogaart 2007. The human immune system (HIS) RAG2-/- c-/- mouse, a novel chimeric mouse model for HIV-1 infection. Clin Vaccine Immunol. 14(4):391-6.
 

Legrand N, Weijer K, Spits H 2008. Experimental model for the study of the human immune system: production and monitoring of "human immune system" Rag2-/-gamma c-/- mice. Methods Mol Biol. 415:65-82.


O ter Brake, N Legrand, KJ von Eije, M Centlivre, H Spits, K Weijer, B Blom and B Berkhout 2009. Evaluation of safety and efficacy of RNAi against HIV-1 in the human immune system (Rag-2-/-c-/-) mouse model. Gene Therapy 16(1):148-53.
 

Ferenc A. Scheeren, Maho Nagasawa, Kees Weijer, Tom Cupedo , Jörg Kirberg, Nicolas Legrand, Hergen Spits 2008. T cell – independent development and induction of somatic hyper mutation in human IgM + IgD + CD27 + B cells. J Exp Med. 205(9):2033-42.

Cupedo T, Crellin NK, Papazian N, Rombouts EJ, Weijer K, Grogan JL, Fibbe WE, Cornelissen JJ, Spits H 2009. Human fetal lymphoid tissue-inducer cells are interleukin 17-producing precursors to RORC+ CD127+ natural killer-like cells. Nat Immunol. Jan;10(1):66-74.

Huntington ND, Legrand N, Alves NL, Jaron B, Weijer K, Plet A, Corcuff E, Mortier E, Jacques Y, Spits H, Di Santo JP 2009. IL-15 trans-presentation promotes human NK cell development and differentiation in vivo. J Exp Med. 206(1):25-34.
 

Nicolas Legrand, Alexander Ploss, Rudi Balling, Pablo D. Becker, Chiara Borsotti, Nicolas Brezillon, Jennifer Debarry, Ype de Jong, Hongkui Deng, James P. Di Santo, Stephanie Eisenbarth, Elizabeth Eynon, Richard A. Flavell, Carlos A. Guzman, Nicholas D. Huntington, Dina Kremsdorf, Michael P. Manns, Markus G. Manz, Jean-Jacques Mention, Michael Ott, Chozhavendan Rathinam, Charles M. Rice, Anthony Rongvaux, Sean Stevens, Hergen Spits, Hélène Strick-Marchand, Hitoshi Takizawa, Anja U. van Lent, Chengyan Wang, Kees Weijer, Tim Willinger and Patrick Ziegler 2009. Humanized Mice for Modeling Human Infectious Disease: Challenges, Progress, and Outlook. Cell Host & Microbe,6(1):5-9
 

Dhivya Haridass, Qinggong Yuan, Pablo D. Becker, Tobias Cantz, Marcus Iken, Michael Rothe, Nidhi Narain, Michael Bock, Miriam Nörder, Nicolas Legrand, Heiner Wedemeyer, Kees Weijer, Hergen Spits, Michael P. Manns, Jun Cai, Hongkui Deng, James P. Di Santo, Carlos A. Guzman and Michael Ott 2009. Repopulation Efficiencies of Adult Hepatocytes, Fetal Liver Progenitor Cells, and Embryonic Stem Cell-Derived Hepatic Cells in Albumin-Promoter-Enhancer Urokinase-Type Plasminogen Activator Mice. American Journal of Pathology 175:1483-1492
 

van Lent AU, Dontje W, Nagasawa M, Siamari R, Bakker AQ, Pouw SM, Maijoor KA, Weijer K, Cornelissen JJ, Blom B, Di Santo JP, Spits H, Legrand N 2009. IL-7 enhances thymic human T cell development in "human immune system" Rag2-/-IL-2Rgammac-/- mice without affecting peripheral T cell homeostasis. J Immunol. Dec 15;183(12):7645-55.
 

Centlivre M, Zhou X, Pouw SM, Weijer K, Kleibeuker W, Das AT, Blom B, Seppen J, Berkhout B, Legrand N 2010. Auto regulatory lentiviral vectors allow multiple cycles of doxycycline-inducible gene expression in human hematopoietic cells in vivo. Gene Ther. Jan;17(1):14-25.
 

van Lent AU, Centlivre M, Nagasawa M, Karrich JJ, Pouw SM, Weijer K, Spits H, Blom B, Legrand N 2010. In vivo modulation of gene expression by lentiviral transduction in "human immune system" Rag2-/- gamma c -/- mice. Methods Mol Biol. 595:87-115.
 

Maijenburg MW, Noort WA, Kleijer M, Kompier CJ, Weijer K, van Buul JD, van der Schoot CE, Voermans C. 2010. Cell cycle and tissue of origin contribute to the migratory behaviour of human fetal and adult mesenchymal stromal cells. Br J Haematol. Feb;148(3):428-40.
 

Scheeren FA, van Lent AU, Nagasawa M, Weijer K, Spits H, Legrand N, Blom B 2010. Thymic stromal lymphopoietin induces early human B-cell proliferation and differentiation. Eur J Immunol. Apr;40(4):955-65.
 

Pablo D. Becker., Nicolas Legrand., Caroline M. M. van Geelen, Miriam Noerder, Nicholas D. Huntington, Annick Lim, Etsuko Yasuda, Sean A. Diehl, Ferenc A. Scheeren, Michael Ott, Kees Weijer, Heiner Wedemeyer, James P. Di Santo, Tim Beaumont, Carlos A. Guzman, Hergen Spits 2010. Generation of Human Antigen-Specific Monoclonal IgM Antibodies Using Vaccinated ‘‘Human Immune System’’ Mice. PLoS One. Oct 4;5(10). pii: e13137.
 

Reijmers RM, Groen RW, Kuil A, Weijer K, Kimberley FC, Medema JP, van Kuppevelt TH, Li JP, Spaargaren M, Pals ST. 2011 Disruption of heparan sulfate proteoglycan conformation perturbs B-cell maturation and APRIL-mediated plasma cell survival. Blood. 2011 Jun 9;117(23):6162-71. Epub Apr 6.
 

Maijenburg MW, Gilissen C, Melief SM, Kleijer M, Weijer K, Brinke AT, Roelofs H, Tiel CM, Veltman JA, Vries CJ, Schoot CE, Voermans C. 2011. Nuclear Receptors Nur77 and Nurr1 Modulate Mesenchymal Stromal Cell Migration. Stem Cells Dev. Jun 1.
 

Kuijpers TW, Ijspeert H, van Leeuwen EM, Jansen MH, Hazenberg MD, Weijer K, van Lier RA, van der Burg M 2011. Idiopathic CD4+ T lymphopenia without autoimmunity or granulomatous disease in the slipstream of RAG mutations. Blood. Jun 2;117(22):5892-6. Epub Apr 18.
 

Huntington N, Alves N, Legrand N, Lim A, Strick-Marchand H, Plet A, Weijer K, Jacques Y, Spits H, Di Santo J 2011. Autonomous and extrinsic regulation of thymopoiesis in human immune system (HIS) mice. Eur J Immunol. Jul 8.
 

Legrand N, Huntington ND, Nagasawa M, Bakker AQ, Schotte R, Strick-Marchand H, de Geus SJ, Pouw SM, Böhne M, Voordouw A, Weijer K, Di Santo JP, Spits H 2011. Functional CD47/signal regulatory protein alpha (SIRP{alpha}) interaction is required for optimal human T- and natural killer- (NK) cell homeostasis in vivo. Proc Natl Acad Sci Aug 9;108(32):13224-9. Epub 2011 Jul 25.
 

Education and training:

1961 - 1968 Faculty of Veterinary Medicine
University of Utrecht, The Netherlands
1966 Veterinary doctorate
1968 Graduated as a veterinarian
1979 Doctoral Thesis (Ph.D.), Faculty of Medicine,
University of Amsterdam, The Netherlands
Thesis: “Feline mammary tumours and dysplasia.
A multidisciplinary study of feline mammary tumours and
dysplasias. Some comparisons with human and canine
mammary tumours and dysplasias”.
1980 -1981 Sabbatical year (6 months), department of pathology
(Head: Prof. Dr. W.F.H. Jarrett), Veterinary School
University of Glasgow, Bearsden, Glasgow, Scotland.
1991 Specialized as Experimental Patho-biologist.
1992 Specialized as Veterinary Pathologist.

Appointments:

1968 - 2002 Staff member, Netherlands Cancer Institute/
Antoni van Leeuwenhoekhuis, department of Immunology
Amsterdam, The Netherlands.
1982 - 1996 Director of B.V. European Veterinary Laboratory EVL, Woerden, The Netherlands.
2002 – date Staff member, Academic Medical Center AMC, department of
Cell biology and Histology.
2006 - 2010 Scientific Director of AMCAS, Amsterdam, The Netherlands.

2011-date Interim manager HIS Mouse Facility of the AMC

 

Other research related activities
  • Board of directors / Trustees / Supervisory board, Biotech