Period at IMGGE: 1986-1994
BSc: Faculty of Biology, University of Belgrade
MSc: Faculty of Biology, University of Belgrade
PhD: University of Belgrade
Current position and address:
Senior Research Associate
Laboratory of Molecular Immunology
1230 York Ave, New York, NY, 10065
- Lymphocytes are the primary effectors of adaptive immunity and assemble a diverse repertoire of immune receptors using a somatic gene recombination process known as V(D)J recombination. This process enables the production of a very large number of unique receptors that are able to recognize almost any antigen. Although V(D)J recombination produces a multitude of antibody receptors, they are relatively low-affinity receptors that must be refined by somatic hypermutation(SHM) and class switch recombination (CSR) to produce the high-affinity antibodies that protect against most pathogens. Majority of human lymphomas are of mature B cell origin and many of them carry balanced chromosomal translocations that involve immunoglobulin genes. This propensity is most likely dependent on Activation-induced cytidine deaminase (AID), the B lymphocyte specific enzyme that initiates class switch recombination (CSR) and somatic hypermutation (SHM).
- My research is focused on molecular mechanisms of CSR and chromosomal rearrangements that are by-product of the physiological recombination reaction. We were able to demonstrate that c-myc/IgH translocations, which are hallmark of Burkitt’s lymphoma, are AID dependent and that double strand DNA breaks at both c-myc and IgH locus are initiated by AID. We generated libraries of rearrangements from B lymphocytes and showed that the key determinants of rearrangements are chromosome territories, active transcription and DNA damage.