MUMMY

The “MUMMY” project (36 months, 2 teams and a private company) will address scientific issues pertinent to the B-cell-lineage and their implications in immunopathology and oncology, with specific focus on antibody-secreting plasma cells. Antibody secreting cells are critical effector cells and long-lived sentinels for immune memory. Plasma cell tumorigenesis results in Multiple Myeloma (MM), a neoplasia characterized by the accumulation of clonal plasma cells within the bone marrow. Recent advances in treatment with the approval of several novel agents and their combinations have significantly improved patient outcome1. However, patients invariably relapse after multiple lines of treatment, with shortened intervals between relapses, and finally become resistant to all treatments, resulting in loss of clinical control over the disease. In this proposal, we seek to are to determine how metabolic alterations during the differentiation of normal B cells into plasma cells contribute to the development of MM, and what metabolomic signatures can be identified that correlate with drug resistance and disease progression. We would like to reveal both the pathways involved in this metabolic remodeling and their downstream effects. The rationale of our project is in line with the identification of major metabolic changes during plasma cell differentiation and in MM cells in association with drug resistance and poor outcome. By leveraging unique cellular models and cutting-edge technologies mastered by the three partners, we aim to uncover metabolic vulnerabilities that can be translated into tangible therapeutic solutions, thereby strengthening our industrial partner’s position in the fields of precision medicine and oncology.