Each year, the American Thyroid Association recognizes the outstanding research contributions of one of its members to a greater understanding of thyroid physiology or the pathophysiology of thyroid disease, with its presentation of The John B. Stanbury Pathophysiology Medal. During the Annual Banquet at its 81st Annual Meeting, the ATA will bestow the 2011 John B. Stanbury Pathophysiology Medal on Basil Rapoport, MB, ChB, Professor and Director of the Thyroid Autoimmune Disease Unit at Cedars-Sinai Medical Center, Los Angeles, CA, and Professor of Medicine at UCLA. The award recognizes the impact that Dr. Rapoport’s research has had on research and clinical practice related to thyroid disease.
Dr. Rapoport has devoted more than 40 years to the study of thyroid pathophysiology, including the molecular cloning of thyroid peroxidase and the thyroid stimulating hormone receptor (TSHR), the main autoantigens involved in autoimmune thyroid disease. His laboratory has also cloned, expressed, and characterized the immunoglobulin genes that code for the repertoire of human thyroid peroxidase autoantibodies, and these have proven to be invaluable tools for the discovery that epitopic recognition of thyroid peroxidase autoantibodies within an immunodominant region of the enzyme is inherited. Dr. Rapoport’s work on the TSHR has provided novel insights into the protein’s structure and function and has demonstrated that receptor intramolecular cleavage involves cleavage at two regions with excision of an intervening portion. A consequence of this cleavage is that one of the two remaining TSHR segments (the A-subunit comprising the leucine-rich repeat domain) is shed from the cell surface. He also overcame a long-standing hurdle in the ability to generate conformationally intact recombinant TSHR protein that is secreted by transfected cells.
The availability of large quantities of recombinant A-subunits contributed to several discoveries in the field, including that the free A-subunit is the primary autoantigen in Graves’ disease, and that genetic immunization with adenovirus vectors expressing the free A-subunit rather than the holoreceptor improves the induced mouse model of Graves’ hyperthyroidism, a modification that is now widely used. The development of this highly effective animal model of Graves’ disease contributed to a number of novel observations, including the role of regulatory T-cells in disease development, the ability of pretreatment with A-subunit to attenuate the development of induced hyperthyroidism, and the localization of genes that influence susceptibility or resistance to induced Graves’ disease.
Dr. Rapoport’s laboratory generated the first TSHR monoclonal antibody with inverse agonist activity. The discovery of an antibody inverse agonist offers the potential to silence TSHR constitutive activity in metastases of well-differentiated thyroid carcinomas, which cannot be achieved with the suppression of thyroid stimulating hormone or the use of thyroid stimulating hormone blocking antibodies.
Dr. Rapoport is a past recipient of the ATA’s Van Meter Award Lecture, and the Sidney H. Ingbar Distinguished Lectureship Award. He is a member of the Editorial Board of Thyroid and has served on the Membership Committee, International Meeting Committee, Program Committee, and Nominating Committee of the ATA.
The American Thyroid Association (ATA) is the leading worldwide organization dedicated to the advancement, understanding, prevention, diagnosis and treatment of thyroid disorders and thyroid cancer. ATA is an international individual membership organization with over 1,400 members from 43 countries around the world. Celebrating its 88th anniversary, ATA delivers its mission through several key endeavors: the publication of highly regarded monthly journals, THYROID, Clinical Thyroidology and Clinical Thyroidology for Patients; annual scientific meetings; biennial clinical and research symposia; research grant programs for young investigators, support of online professional, public and patient educational programs; and the development of guidelines for clinical management of thyroid disease. Visit www.thyroid.org for more information.