Researchers' Proposals
Ligand binding to receptors on immuncompetent cells mediates signals, which trigger complex biochemical pathways, ultimately leading to the antigen specific response of the cells. My main interest is the regulation of the immune response, in particular the exploration of receptor-triggered signaling pathways leading to cell survival, cell activation or programmed cell death of B lymphocytes.
The B cell receptor complex (BCR) and the co-receptors, such as the receptors specific for the Fc part of immunoglobulin G (FcγRIIb) control the positive and negative selection of B cells. The rate of expression, as well as the homo- and heteroaggregation of receptors has a determining role in the cells’ response. Co-aggregation of BCR and FcγRIIb by immunocomplexes represents an autocrin, negative feedback regulation loop, the integrity of which is important to block inadequate cell activation. The failure of this function may lead to the development of autoimmune diseases. We study the signaling under normal and pathological conditions, in particular in B cells from patients with autoimmune diseases.
Receptor aggregation leads to the activation of protein and lipid kinases and phosphatases, and the reorganization of the cell membrane. Signals arising from different receptors are integrated, resulting in the triggering of various signaling pathways, leading to either cell activation, survival or programmed cell death. The differences between these pathways are not clarified yet. We study the “cross-talk” between the activating and inhibitory receptors on B cells at different stages of maturation: the activity of kinases and phosphatases, the role of serine phosphorylation, protein-protein interactions, and the activation of transcription factors.