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Dr Febe van Maldegem

Research Interests

 

In response to an infection, our body starts producing antibodies that bind to the pathogen. These antibodies gain their high affinity and specificity by maturation through modifications on the level of our DNA. These processes need to be tightly controlled, as mistakes can be detrimental.

During my PhD in the AMC in Amsterdam, I have studied the consequences of such mistakes, where mutations in the DNA have led to the development of mature B cell lymphomas. We aimed to understand what sort of immune response allows for the occurrence of such mistakes, by looking at the inflammatory environment in which the lymphomas have arisen. And we have looked for commonalities in the antigen binding site of the antibodies, to see whether the origin of these lymphomas can be traced back to certain infections.

Currently, as a Post-doctoral researcher in the MRC-LMB in Cambridge, I study the molecular processes that underlie the DNA modifications required for antibody maturation. We investigate the control mechanisms that are in place to prevent mistakes. We identify new proteins that are be part of this control mechanism, and try to understand how they function in this complex network of regulation.

In future I hope to bring both fields of research together, by taking the knowledge from the molecular biology of antibody maturation and translate it into the field of lymphoma-research. Ultimately, this may provide us with new targets for therapy.

 

 

Keywords

B cells ; germinal center ; antibody maturation ; somatic hypermutation ; memory cells

Key Publications

Ganesh K, van Maldegem F, Telerman SB, Simpson P, Johnson CM, Williams RL, Neuberger MS, Rada C. Structural and mutational analysis reveals that CTNNBL1 binds NLSs in a manner distinct from that of its closest armadillo-relative, karyopherin α. FEBS letters. 2014 Jan; 588(1):21-7

Chandra A, van Maldegem F, Andrews S, Neuberger MS, Rada C. Deficiency in spliceosome-associated factor CTNNBL1 does not affect ongoing cell cycling but delays exit from quiescence and results in embryonic lethality in mice. Cell Cycle. 2013 Mar 1;12(5):732-42

van Maldegem F, Wormhoudt TAM, Mulder MMS, Oud MECM, Schilder-Tol E, Musler AR, Aten J, Saeed P, Kersten MJ, Pals ST, van Noesel CJM, Bende RJ. Chlamydia psittaci-negative ocular adnexal marginal zone B-cell lymphomas have biased VH4-34 immunoglobulin gene expression and proliferate in a distinct inflammatory environment. Leukemia. 2012 Jul;26(7):1647-53.

van Maldegem F, Jibodh RA, van Dijk R, Bende RJ, van Noesel CJM. Activation-induced cytidine deaminase splice variants are defective due to the lack of structural support for the catalytic site. Journal of Immunology. 2009; 184(5):2487-91.
van Maldegem F, Scheeren FA, Jibodh RA, Bende RJ, Jacobs H, van Noesel CJM. AID splice variants lack deaminase activity. Blood. 2009;113:1862-1864.
Bende RJ, van Maldegem F, van Noesel CJM. Chronic inflammatory disease, lymphoid tissue neogenesis and extranodal marginal zone B-cell lymphomas. Haematologica. 2009;94:1109-1123.
van Maldegem F, van Dijk R, Wormhoudt TAM, Kluin PM, Willemze R, Cerroni L, van Noesel CJM, Bende RJ. The majority of cutaneous marginal zone B-cell lymphomas expresses class-switched immunoglobulins and develops in a T-helper type 2 inflammatory environment. Blood. 2008;112:3355-3361.
Bende RJ, van Maldegem F, Triesscheijn M, Wormhoudt TAM, Guijt R, van Noesel CJM. Germinal centers in human lymph nodes contain reactivated memory B cells. J Exp Med. 2007;204:2655-2665.