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