Targeting the LIM and SH3 domain protein (Lasp)1 to modulate fibroblast-like synoviocytes (FLS)- mediated pathologies in rheumatoid arthritis (RA)

• Applicants: Dr. Denise Beckmann; Dr. Adelheid Korb-Pap
• Subject Area: Rheumatology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 574956288

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by the progressive destruction of articular structures, especially cartilage and bone. Fibroblast-like synoviocytes (FLS) are important effector cells in RA and contribute significantly to the transformation of the synovial membrane into an inflamed, hyperplastic, and aggressive tissue that invades adjacent joint structures. Recent data indicate that LIM and SH3 domain protein (Lasp1) is prominently induced in RA-FLS and plays a crucial role in regulating their cytoskeletal dynamics and aggressive transformation. Preliminary results suggest that an inhibitory peptide can replicate the phenotype of Lasp1 knockout cells, providing a potential therapeutic approach. This project aims to clarify how Lasp1 drives the tumor-like phenotype of FLS and to identify its interaction partners that contribute to FLS-mediated pathologies in RA. Using recently generated conditional Lasp1 deficient mice along with gene expression analyses, protein interaction studies, cytoskeletal dynamics assays, and functional and inflammatory marker analyses, we will gain novel and detailed insights into the role of Lasp1 in RA pathogenesis. In addition, we will use a novel, patented targeting technology to assess the potential of Lasp1 antisense oligonucleotides and specific inhibitory peptides for the treatment of RA-like disease in murine models.

• DFG Programme: Research Grants
• International Connection: Austria, Sweden
• Cooperation Partners: Professor Dr. Daniel Aletaha; Dr. Mattias Svensson