The main focus of our research laboratory at the James J Peters VA Medical Center is thyroid autoimmune disease with the TSH receptor as the key molecule of interest. The TSH receptor (TSHR), a G protein coupled receptor on the basolateral surface of the thyrocytes, regulates thyroid growth and metabolism. Incidentally, it is also the major auto antigen in human autoimmune thyroid disease such as Graves' disease (autoimmune hyperthyroidism). The laboratory studies various aspects of the TSH receptor including its genetic association with disease, the multiple post translational changes it undergoes and the important role, of TSHR antibodies in thyroid autoimmune disease. In addition we have developed major activity in the areas of thyroid stem cells and the role of extra thyroidal TSHRs found in osteoclasts and osteoblasts. These studies are funded by the National Institutes of Health, the VA Merit Award Program, the Mount Sinai School of Medicine and the James J. Peters VA Medical Center.