PHOSPHOLAMBAN AND HYPOTHYROID AND HYPERTHYROID HEARTS

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My research goal under the Fogarty Fellowship would be to clarify the regulatory role of phospholamban on the SR Ca2+-pump in various thyroid states (hypothyroid, euthyroid and hyperthyroid). These studies will provide an appropriate approach to the determination of the role of phospholamban in regulation of the SR function in thyroid hearts and its involvement in mediating the altered response of these hearts to Beta- adrenergic stimulation. Such studies may provide the basis for an approach to the treatment of thyroid disease with more rational experiments. At Albert Szent-Gyorgyi Medical University in Hungary I work in cooperation with a clinical cardiologist and plan to start biochemical studies on cardiomyopathic heart muscle. Accordingly, the various biochemical techniques with which the SR function can be studied under in vitro and in vivo conditions (SR preparation, characterization, purificatioin of phospholamban, reconstitution of SR membrane vesicles, measurement of Ca2+ uptake and Ca2+-ATPase activity, radioimmunoassay techniques, heart perfusion, etc.) would be extremely important for me. At Prof. Kranias's laboratory in Cincinnati, I have a very good chance to master all of these methods, since all of the necessary equipment is available and good experts can help me to become familiar with all of the relevant techniques.