Molecular Mechanisms of Membranous Nephropathy – New Avenues Towards an Individualized Therapy

• Applicant: Dr. Nicola Tomas
• Subject Area: Nephrology
• Term: since 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 405934253

Several important aspects of the initially proposed work programme could be addressed until now, particularly in relation to the translational characterization of the pathogenic role of the complement system in MN as well as the development of antigen-specific disease models. Moreover, key proof-of-concept investigations regarding MN pathomechanisms and the establishment of antigen-specific treatments were performed. On the basis of this previous work, it is now possible to refine and deepen the analyses. In a potential sixth year of funding, the proposed project will capitalize on the unique models and tools that are exclusively available in the group in order to: 1. Understand the function of the highly conserved podocyte protein THSD7A in podocytes. 2. Characterize the signaling networks that mediate complement-independent podocyte damage in THSD7A-associated MN using single-nucleus RNA-sequencing (snRNA-seq), proteomics, biochemical, and histological analyses. 3. Further investigate antigen-specific treatment strategies aiming at the removal of pathogenic autoantibodies through endogenous degradation systems in the liver and depletion of antigen-specific B cells using chimeric autoantibody receptor (CAAR) NK and T cells.

• DFG Programme: Independent Junior Research Groups