The general research area of my laboratory is transport across biological membranes with an emphasis on structure/function relationships of membrane proteins. A major topic is the characterization of the sodium/iodide symporter, the protein that mediates the accumulation of iodide in the thyroid gland. Iodide uptake is the first step in the biosynthesis of the thyroid hormones T3 and T4. Although the remarkable capability of the thyroid for iodide uptake is well established, almost no detailed molecular information on the symporter is available. Efforts are directed at identifying the cDNA that encodes the sodium/iodide symporter by functional screening of cDNA libraries. Biochemical, biophysical and immunological approaches are being used to identify the symporter. The findings of these studies will help elucidate some of the molecular changes that occur in thyroid cancer and in congenital lack of iodide accumulation, a condition that leads to hypothyroidism and cretinism. Our studies on the regulation of the thyroid sodium/iodide symporter have revealed that the protein is activated by proteolysis, and that stimulation of iodide accumulation by thyroid stimulating hormone (TSH) involves not only increased biosynthesis but also activation of the symporter. We have discovered, both in vivo and in vitro, that TSH regulates the thyroidal expression of calnexin, a molecular chaperone that assists in proper folding of nascent proteins in the endoplasmic reticulum (ER). This is the first factor identified as a calnexin regulator. Interactions of calnexin with various thyroid proteins are being examined.