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 inhibiting the RAD51 pathway has the potential to effectively and selectively target AID+ disease causing cells in autoimmune disorders such as lupus and type 1 diabetes. 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 a wide range of autoimmune disorders.
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.