Objective Human B cell lymphomas including multiple myeloma and Hodgkin¿s disease are frequent malignancies and a major clinical problem. Their high incidence is due to special features of normal B cell development that promote chromosomal translocations and other genetic alterations. Another contributing factor is Epstein-Barr-Virus (EBV), a B cell-transforming virus endemic in humans. EBV-infected cells are usually eliminated by the immune system, but in immunosuppressed (post-transplant or AIDS) patients, EBV infection spreads and drives lymphomagenesis.We have generated a novel genetic tool that allows us to introduce combinations of loss- and gain-of-function mutations specifically into B cells in the mouse, to analyze the cooperation of oncogenic factors thought to contribute to B lymphomagenesis in humans. The unique feature of this method is that only a small fraction of cells is mutated (mimicking the sporadic nature of somatic cancerogenesis) and that cells having acquired either single or combined mutations can be observed side-by-side.Using a large set of mutant alleles, we will test whether the interplay of certain combinations of survival, proliferation and differentiation signals determines the development of different classes of human B cell malignancies. A special focus is on Hodgkin¿s disease, where EBV infection and genetic reprogramming play a critical role. We will also investigate the mechanism of immune surveillance of EBV-infected B cells and EBV-driven B cell lymphomas.Ultimately we hope to elucidate key pathways of lymphoma pathogenesis, identify novel contributing mutations, and generate preclinical mouse models to assess therapeutic strategies and mechanisms of tumor immune surveillance. Fields of science natural sciencesbiological sciencesmicrobiologyvirologymedical and health sciencesbasic medicineimmunologymedical and health scienceshealth sciencesinfectious diseasesRNA virusesHIVnatural sciencesbiological sciencesgeneticsmutation Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-AG-LS6 - ERC Advanced Grant - Immunity and infection Call for proposal ERC-2010-AdG_20100317 See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Coordinator MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC) Address Robert rossle strasse 10 13125 Berlin Germany See on map Region Berlin Berlin Berlin Activity type Research Organisations Administrative Contact Ioannis Legouras (Dr.) Principal investigator Peter Klaus Georg Rajewsky (Prof.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC) Germany EU contribution € 2 487 787,00 Address Robert rossle strasse 10 13125 Berlin See on map Region Berlin Berlin Berlin Activity type Research Organisations Administrative Contact Ioannis Legouras (Dr.) Principal investigator Peter Klaus Georg Rajewsky (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data
