Immunomodulatory effects of Staphylococcal aureus Protein A / Immunoglobulin G complexes and their potential as a therapeutic for the treatment of osteolytic bone disease

• Applicant: Dr. Katja Thümmler
• Subject Area: Rheumatology
• Term: from 2010 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 190974745

Many diseases including multiple myeloma (MM) and rheumatoid arthritis (RA) are associated with bone erosion due to increased numbers and activity of osteoclasts, and there is a desperate need for novel treatment strategies targeting this aspect of pathogenesis. In preliminary studies, it was shown that highly purified complexes of Staphylococcal aureus Protein A and Immunoglobulin G (SIC) can inhibit osteoclastogenesis and drive macrophages to an anti-inflammatory phenotype. This fellowship will dissect the mechanism underlying the immunomodulatory effects of SIC, and determine its potential as a therapeutic for diseases such as MM and RA. This will involve a human in vitro osteoclastogenesis culture system and a myeloma cell / pre-osteoclast co-culture system in the presence or absence of SIC. In addition, osteoclast intracellular signaling pathways altered by SIC will be investigated in both systems. Together these studies will significantly increase our understanding on the pathological mechanisms of bone erosions associated with MM. The proposed studies will validate SIC as a potent inhibitor of osteoclastogenesis. Providing insights into the development of therapeutics for the treatment of osteolytic bone disease either directly through SIC treatment or by identifying the key signaling cascade that can be targeted via other means to alter osteoclastogenesis.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Professor Dr. Carl S. Goodyear