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Prof Marieke (S. M.) van Ham PhD

Training

Medical Microbiology and Immunology, University of Amsterdam

Thesis

Genetic and functional studies of Haemophilus influenzae fimbriae 1994 - University of Amsterdam  and Max-Planck-Institute for Biology (Germany) 

Research interests

We investigate in human how B cell differentiation into IgG-secreting plasma cells (PC) is regulated by antigen and specific signals from follicular Thelper cells. We identified the first known linear Bn->PC differentiation pathway in vitro using scRNAseq and now focus on novel cell surface differentiation markers and unknown regulators that identify the various stages of B cell to plasma cell formation in vitro and in vivo. We use big data analyses and systems biology to unravel integrated networks of immune regulation. This knowledge is important to prevent alloantibody formation (RhD and sickle cell disease), to intervene against autoantibodies in autoimmune diseases (MS/vasculitis/pemphigus/SLE/RA) or to understand occurrence of humoral immunodeficiencies. In addition, it may aid to optimise Sanquin’s hyperimmunization protocols to generate specific immunoglobulins (RhD/HepA/TT) and vaccination protocols in general. Our research is linked to Sanquins’ medical needs Immunodeficiency and Aging, Vascular Diseases and Inflammation and Anemia. See also Antigen specific B cell responses

 

Technology

  • B cell differentiation assays (both T cell-dependent and –independent)
  • Single cell and bulk RNA sequencing technology
  • CRISPR-Cas9 technology in primary B cells
  • BCR/TCR clonality analyses
  • Antigen-specific CD4+ T cell priming and recall analyses
  • Identification of T cell epitopes
  • Antibody assays
  • Multi-color flow cytometry (phenotype and function)
  • Imagestream and confocal analyses

 

Resume

 

2016-present

Board member Dutch Society for Immunology (NVVI) and President of 5th European Congress of Immunology (2018)

2010-present

Professor of Biological Immunology, Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam,

2005-present

Head department of Immunopathology, Sanquin, Amsterdam

2003-2004

Group leader, department of Immunopathology, Sanquin, Amsterdam

2000-2003

Assistant and Associate Professor, Head Unit Experimental Oncopathology, Free University Medical Center

1997-2000

Postdoc, division of Tumor Biology, Netherlands Cancer Institute, Amsterdam (group. J.J. Neefjes)

1994-1997

Scientific staff member, Human Immunogenetics Laboratory, Imperial Cancer Research Fund, London, United Kingdom

Other activities

  • Responsible for Immunology Curriculum Bachelor Biomedical Sciences and Master of Life Sciences.
  • Coordinator/lecturer Immunology courses, 2nd-3rd year medical students, Faculty of Medicine, Anton de Kom University (AdeKU), Suriname
  • Ad hoc speaker and advisor for general public about topics concerning functioning of immune system and/or vaccination.

Other publications

Van Alphen L, van Ham M, Geelen-van den Broek L, and Pieters T. Relationship between secretion of the Anton blood group antigen in saliva and adherence of Haemophilus influenzae to oropharynx epithelial cells. FEMS Microbiol. Immunol 1989; 1:357.

Van Ham SM, Mooi FR, Sindhunata MG, Maris WR, and van Alphen L. Cloning and expression in Escherichia coli of Haemophilus influenzae fimbrial genes establishes adherence to oropharyngeal epithelial cells. EMBO J 1989; 8:3535.

Van Alphen L, Geelen-van den Broek L, and van Ham M. In vivo and in vitro expression of outer membrane components of Haemophilus influenzae. Microb Pathog 1990; 8:279.

Van Alphen L, Geelen-van den Broek L, Blaas L, van Ham M, and Dankert J. Blocking of fimbria-mediated adherence of Haemophilus influenzae by sialyl gangliosides. Infect Immun 1991; 59:4473.

Van Ham SM, van Alphen L, and Mooi FR. Fimbria-mediated adherence and hemagglutination of Haemophilus influenzae. J Infect Dis 1992; 165:S97.

Van Ham SM, van Alphen L, Mooi FR, and. van Putten JP. Phase variation of H. influenzae fimbriae: transcriptional control of two divergent genes through a variable combined promoter region. Cell 1993; 73:1187.

Van Ham SM, van Alphen L, Mooi FR, and van Putten JP. The fimbrial gene cluster of Haemophilus influenzae type b. Mol Microbiol 1994; 13:673.

Van Alphen L, and van Ham SM. Adherence and invasion of Haemophilus influenzae. Rev Med Microbiol 1994; 5:245.

Davies J, Carlstedt I, Nilsson AK, Hakansson A, Sabharwal H, van Alphen L, van Ham M, and Svanborg C. Binding of Haemophilus influenzae to purified mucins from the human respiratory tract. Infect Immun 1995; 63:2485.

Van Ham SM, van Alphen L, Mooi FR, and van Putten JP. Contribution of the major and minor subunits to fimbria-mediated adherence of Haemophilus influenzae to human epithelial cells and erythrocytes. Infect Immun 1995: 63:4883.

Beck S, Belich M, Grüneberg U, Jackson A, Kelly A, Sanseau P, Sanderson F, Trowsdale J, and van Ham M. Organisation and functions of class II genes and molecules. DNA Seq. 1996; 7:21.

Van Ham SM, Grüneberg U, Malcherek G, Bröker I, Melms A, and Trowsdale J. Human histocompatibility leukocyte antigen (HLA)-DM edits peptides presented by HLA-DR according to their ligand binding motifs. J Exp Med.1996; 184:2019.

Grüneberg U, van Ham SM, Malcherek G, Bröker I, Melms A, and Trowsdale J. The structure and function of the novel MHC class II molecule, HLA-DM. Biochem Soc Trans 1997; 25:208S.

Grüneberg U, Rich T, Roucard C, van Ham SM, Charron D, and Trowsdale J. Two widely used anti-DR alpha monoclonal antibodies bind to an intracellular C-terminal epitope. Hum Immunol 1997; 53:34.

Van Ham SM, Tjin EPM, Lillemeier BF, Grüneberg U, van Meijgaarden KE, Pastoors L, Verwoerd D, Tulp A, Canas B, Rahman D, Ottenhoff TH, Pappin DJ, Trowsdale J, and Neefjes J. HLA-DO is a negative modulator of HLA-DM-mediated MHC class II peptide loading. Curr Biol 1997; 7:950.

Ullrich H.J, Döring K, Grüneberg U, Jähnig F, Trowsdale J, and van Ham SM. Interaction between HLA-DM and HLA-DR involves regions that undergo conformational changes at lysosomal pH. Proc Natl Acad Sci U.S.A. 1997; 94:13163.

Geluk F, Eijk PP, van Ham SM, Jansen HM, and van Alphen L. The fimbria gene cluster of nonencapsulated Haemophilus influenzae. Infect Immun 1998; 66:406.

Hitzel C, Grüneberg U, van Ham M, Trowsdale J, and Koch N. Sodium dodecyl sulfate-resistant HLA-DR "superdimer" bands are in some cases class II heterodimers bound to antibody. J Immunol 1999; 162:4671.

Van Ham M, van Lith M, Lillemeier B, Tjin E, Grüneberg U, Rahman D, Pastoors L, van Meijgaarden K, Roucard C, Trowsdale J, Ottenhoff T, Pappin D, and Neefjes. J Modulation of the MHC class II-associated peptide repertoire by HLA-DO. J Exp Med 2000; 191:1127.

Van Ham M, van Lith M, Griekspoor A, and Neefjes J. What to do with HLA-DO? Immunogenetics 2000; 51:765. Review.

Van Lith M, van Ham M, Griekspoor A, Tjin E, Verwoerd D, Calafat J, Janssen H, Reits E, Pastoors L, and Neefjes J. Regulation of MHC class II antigen presentation by sorting of recycling HLA-DM/DO and class II within the multivesicular body. J Immunol 2001; 167:884.

Roucard C, Thomas C, Pasquier M-A, Trowsdale J, Sotto J-J, Neefjes J, and van Ham M. In vivo and in vitro modulation of HLA-DM and HLA-DO is induced by B lymphocyte activation. J Immunol 2001; 167:6849.

Van Lith M, van Ham M, and Neefjes J. Novel polymorphisms in HLA-DOA and HLA-DOB in B cell malignancies. Immunogenetics 2002; 54:591.