New Targets of Thyroid Hormone Action


Thyroid hormone is major regulator of body weight and metabolic status in humans. Despite its prominent role in normal human function and in replacement therapy our ability to determine its beneficial effects are limited as our diagnostic tests have remained similar for 50 years. The goal of this application is to use novel biochemical and genetic platforms to better understand thyroid hormones beneficial effects on metabolism in order to better tailor replacement therapy in patients and to aid in the development of novel therapies for metabolic disease.

Thyroid Follicular Cell Development in Mice and Humans


Thyroid hormone (TH) is a critical mediator of fetal development and then essential for normal health during adulthood. Currently, therapy for those with hypothyroidism (either congenital or acquired later in life) is with L-thyroxine and many individuals on therapy do not feel adequately replaced. In this proposal we put forward experiments designed to develop thyroid hormone secreting follicular cells from mouse embryonic stem cells and human induced pluripotent stem cells. Completion of this work will give us significant insight into the developmental biology of the thyroid and potentially offer a unique and powerful approach to treat hypothyroidism in humans. Furthermore, the development of follicular cells from progenitor cells will give us an ideal model to better understand many disease of the thyroid that affect human health.

Corepressor Regulation of Nuclear Receptor Action


Thyroid hormone (TH) is a critical mediator of fetal development and then essential for normal metabolic and neurologic function during adulthood. Over the last number of years it has become increasingly clear that tissue-specific actions of TH are likely more important to determine rather than a global assessment of thyroid function. To do this one must understand the components of the complex that determines cellular TH action. This proposal will focus on key components of that complex the nuclear corepressors, NCoR1 and SMRT and show how they mediate key cell-specific effects to mediate TH action.

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