Emergence of synthetic lethality as a paradigm for treating autoimmune disease.
Our scientists have contributed to the discovery of previously unexpected roles for DNA repair in the pathogenesis of autoimmune diseases. Together with our collaborators we found that AID and RAD51 represent a targetable synthetic lethal gene pair in autoimmunity, just as in cancer.
We found that RAD51 modulation effectively targets AID+ disease-mediating cells, effectively blocking the progression of diseases such as T1D and SLE. Our latest data suggest a highly novel immunomodulatory effect in which treatment induces the expansion of a beneficial and protective cell type. This effect may promote stable, long-term disease suppression, which has potential applications for other autoimmune disorders including rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease.
An example of synthetic lethality to treat autoimmunity: Type 1 diabetes
In Type 1 diabetes, autoreactive B-lymphocytes recognize self-antigen, induce AID and activate T-lymphocytes to destroy insulin producing cells. Elimination of autoreactive B-lymphocytes can reduce T-lymphocyte activation, preventing destruction of pancreatic cells.