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Prof. dr. R.A.W. van Lier

Main activities
Research
Focus of research

The unifying theme of my research program is the regulation of effector/memory T cell formation in human and mice. The goals are to (1) identify functionally distinct T-cell subsets, (2) study the regulation of their specificity, expansion and effector functions, and (3) define their roles in normal and pathological immune reactions, e.g. (persistent) virus infections, allo-reactivity and immunodeficiency. Detailed knowledge on the regulation and manipulation of T cell immunity is necessary to improve the design of vaccines for infectious and malignant disease.
 

Key publications
  • Hombrink P, Helbig C, Backer RA, Piet B, Oja AE, Stark R, Brasser G, Jongejan A, Jonkers RE, Nota B, Basak O, Clevers HC, Moerland PD, Amsen D, van Lier RAW, Programs for the persistence, vigilance and control of human CD8(+) lung-resident memory T cells. NAT IMMUNOL 2016;17 (12):1467-1478 [PubMed]
  • Vieira Braga FA, Hertoghs KML, Kragten NAM, Doody GM, Barnes NA, Remmerswaal EBM, Hsiao CC, Moerland PD, Wouters D, Derks IAM, van Stijn A, Demkes M, Hamann J, Eldering E, Nolte MA, Tooze RM, ten Berge IJM, van Gisbergen KPJM, van Lier RAW, Blimp-1 homolog Hobit identifies effector-type lymphocytes in humans. EUR J IMMUNOL 2015;45 (10):2945-2958 [PubMed]
  • van Gisbergen KPJM, Kragten NAM, Hertoghs KML, Wensveen FM, Jonjic S, Hamann J, Nolte MA, van Lier RAW, Mouse Hobit is a homolog of the transcriptional repressor Blimp-1 that regulates NKT cell effector differentiation. NAT IMMUNOL 2012;13 (9):864-871 [PubMed]
  • Klarenbeek PL, Remmerswaal EBM, ten Berge IJM, Doorenspleet ME , van Schaik BDC, Esveldt REE, Koch SD, ten Brinke A, van Kampen AHC, Bemelman FJ, Tak PP, Baas F, de Vries N, van Lier RAW, Deep sequencing of antiviral T-cell responses to HCMV and EBV in humans reveals a stable repertoire that is maintained for many years. PLOS PATHOG 2012;8 (9):e1002889 [PubMed]
  • van Gisbergen KPJM, Klarenbeek PL, Kragten NAM, Unger PPA, Nieuwenhuis MBB, Wensveen FM, ten Brinke A, Tak PP, Eldering E, Nolte MA, van Lier RAW, The costimulatory molecule CD27 maintains clonally diverse CD8(+) T cell responses of low antigen affinity to protect against viral variants. IMMUNITY 2011;35 (1):97-108 [PubMed]
All Publications
Curriculum Vitae

 Academic record
 

1983: MD, University of Amsterdam 

1988: PhD, Title thesis: ‘The Immunobiology of T cell Membrane Molecules’, University of Amsterdam

1990-1995: Fellow of the Royal Dutch Academy of Arts and Sciences (KNAW)

1995-1999: Head of the laboratory for Cellular Immunology, department of Clinical Viro-Immunology, CLB (now Sanquin), Amsterdam 

1999-2000: Head of the department of Immunobiology, CLB, Amsterdam 

2000 - : Professor of Experimental Immunology, University of Amsterdam

2001 - 2010 : Head of the department of Experimental Immunology, Academic Medical Centre (AMC), Amsterdam

2006 - 2010:  vice-chairman of the division of Laboratory Science, AMC

2007-2013: Chairman of the Dutch Society for Immunology (NVVI)

2006 -2011 : Chairman AMC Research Council

2010-: Member of the Executive Board and Director of Research, Sanquin Blood foundation, Amsterdam 

2012:  President-elect of the European Federation of Immunological Societies (EFIS)

Research programmes

Molecular basis of T cell differentiation

Immune activation induces a strong expansion of antigen-specific T cells that acquire effector functions and control spread of invading pathogens. During recovery from infection most activated T cells die but a fraction remains and returns to a resting state. These memory cells provide improved immunological protection to a future challenge with the same pathogen. Our studies have two aims:

1 To clarify the role of TNF-R superfamily members in regulating effector, memory and regulatory T cell formation in vivo. For these studies we have generated a unique series of transgenic mice that overexpress the specific ligands for two receptors i.e. CD27 and GITR.

2 To delineate genetic programs that direct CD8+ T cell differentiation and test if interference with particular differentiation pathways impedes establishment of immunological memory. To identify genes that are expressed during specific differentiation stages transcriptomes of CD8+ T cell subsets were compared by Agilent® micro array analyses and 267 genes were selected that were significantly up or downregulated in effector-type cells compared to naïve and/or memory-type cells. Importantly an evolutionary-conserved novel transcription factor was identified that appears to selectively expressed in cytolytic T cells and NK cells. The function of this factor is currently being analyzed.

This research group participates in CINIMA and CIA

Faculty
Prof. dr. R.A.W. van Lier (Sanquin)

Postdocs
Dr. P. Hombrink (Sanquin)
Dr. R. Stark (Sanquin)

PhD Students
F.M. Behr MSc
Drs. L.C. Berkhout (Sanquin)
A. Chuwonpad
J.J. Freen-van Heeren MSc (Sanquin)
J. Koers
C. Marsman
B.P. Nicolet
A.E. Oja
R. Opstelten
L. Schimmel
J. Steuten
R.L.R.E. Taggenbrock
Drs. N.J.M.C. Verstegen
M.L. Vidal
A.A. de Waard
N.D. Zandhuis

Others
Drs. N.A.M. Kragten (Sanquin)

Prof. dr. R.J.M. ten Berge (Transplantation Immunology)

Other research related activities
  • Membership of medical or scientific committee, Astmafonds, Scientific Advisory Board
  • Membership of medical or scientific committee, Stichting MS Research, Scientific Advisory Board
  • Membership of medical or scientific committee, LSBR, Scientific Advisory Board
  • Membership of editorial board / Editorship, IMMUNOLOGY LETTERS
  • Membership of editorial board / Editorship, EUROPEAN JOURNAL OF IMMUNOLOGY