Research Interests

The Bottini laboratory focuses on protein tyrosine phosphatases (PTP), a large family of enzymes which play an important role in signaling regulation. PTPs are drug targets for autoimmunity, cancer, infections, and metabolic diseases. The laboratory is interested in understanding the role of PTPs in human disease, in particular autoimmune diseases such as Type 1 Diabetes (T1D), Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE) and others. There is strong emphasis on studying disease-relevant problems including the possible validation of PTPs as drug targets for human autoimmune diseases. Well-established collaborations with domestic and international scientists enable the laboratory to apply a wide range of approaches ranging from protein chemistry to cell biology/biochemistry to in vivo work on mouse models.

In the Bottini laboratory, a major research line is focused on the role of the lymphoid tyrosine phosphatase (LYP) in T1D. LYP is a cytosolic phosphatase encoded by the gene PTPN22. Dr. Bottini had discovered that a genetic variant in PTPN22 predisposes humans to T1D. The same variant also increases risk of RA, SLE, and other autoimmune diseases. The Bottini laboratory has been studying the role of LYP in various cellular signaling pathways, its molecular regulation, and its possible mechanism of action in the pathogenesis of T1D. Work on LYP in the Bottini laboratory is currently funded by the NIH and relies on numerous collaborations with intramural LIAI laboratories, and with outside laboratories.

A second research line focuses on development of new assays for detection of phosphatase activity with the objective to aid in development of novel types of cell permeable phosphatase inhibitors. This project is a tight collaboration with the laboratory of Dr. Amy Barrios at the University of Utah, and is currently funded by a joint grant from the NIH. Other key collaborators are Dr. Rekha Panchal at USAMRIID, and Dr. Zhong-Yin Zhang at Indiana University.

A third research line focuses on the role of PTPs in RA, and it is carried out in collaboration with Dr. Gary Firestein and Dr. Maripat Corr from UCSD Rheumatology. This project has an in vivo emphasis and makes use of mouse models of RA.