Adaptor proteins in signal transduction, leukocyte signalling, autoinflammatory diseases, common variable immunodeficiency
The Laboratory of Leukocyte Signalling is studying the molecular mechanisms of signal transduction in leukocytes. Our interest has recently been focused on proteins that regulate signal transduction and immune responses in myeloid cells, such as granulocytes, macrophages and dendritic cells. We are particularly interested in the so called membrane adaptor proteins. These are either transmembrane or membrane-associated proteins responsible for the recruitment of networks of signalling molecules to the proximity of cellular membranes. Some of the members of this group have key roles in the propagation of the signal generated by leukocyte surface receptors (e.g. transmembrane adaptor LAT), while others have more complex or negative regulatory functions (e.g. PAG and many others). Currently we are studying several incompletely characterized proteins from the latter category. Among the most interesting is the membrane associated adaptor protein PSTPIP2. In the mouse model, mutations in Pstpip2 gene, which result in the absence of the corresponding protein, lead to the development of chronic multifocal osteomyelitis. It is an autoinflammatory disease characterized by spontaneous bone and skin inflammation which closely resembles several human disorders. We are studying the molecular mechanisms of how the complex of proteins organized by PSTPIP2 regulates inflammatory processes and how its absence leads to an impaired control of inflammation. Another protein we are extensively studying is transmembrane adaptor SCIMP. It is expressed specifically in professional antigen-presenting cells, where it participates in MHCII-dependent reverse signalling. Recently we have found that it is also involved in the propagation of signalling through an important receptor for pathogenic fungi Dectin-1. Finally, we are also conducting research aiming at uncovering the relationship between signal transduction and leukocyte-driven pathologies. Projects within this area include studies of signalling proteins aberrantly expressed in childhood leukaemias and research of changes in leukocyte signal transduction in patients with Common Variable Immunodeficiency (CVID), both running in collaboration with clinical laboratories.
Last change: February 22, 2016