The Bottini laboratory studies the mechanism of action of signaling molecules encoded by human autoimmune disease-predisposing genes and also analyzes signal transduction pathways in pathological specimens from patients. The goal is to dissect relevant intracellular pathways to design new methods for disease activity monitoring and to identify new treatment strategies. The laboratory specializes in the study of a family of signaling enzymes called protein tyrosine phosphatases, which regulates phosphorylation of proteins on tyrosine residues.
The first focus of the laboratory is on phosphatase genes that increase risk of autoimmune disease. Dr. Bottini was the first to report that a mutation in the PTPN22 gene, encoding a phosphatase, increases the risk of autoimmunity in humans. Currently PTPN22 is ranked as a major gene for rheumatoid arthritis, juvenile diabetes, and lupus. Dr. Bottini’s laboratory is focused on understanding the mechanism of action and regulation of PTPN22 with the goal of developing personalized ways to treat disease in carriers of autoimmune-predisposing gene variants.
A second focus of the laboratory is on studying biochemical signaling (focusing in particular on the role of phosphatases) in tissue resident cells in arthritis, scleroderma and other diseases. The goal is to develop ways to inhibit the disease promoting action of these cells to help control disease activity without depressing the ability of the immune system to fight against infections and tumors.