Regulation Mechanisms of Thyroid Hormone Receptors in the Heart

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DESCRIPTION (provided by applicant): Dr. Ledee is an experienced research and well published. She is presently a research scientist in the laboratory of Dr. Michael Portman. She is responsible for many projects including: 1) Investigating changes in metabolic proteins post mechanical circulatory support by extracorporeal membrane oxygenation after thyroid hormone treatment or weaning. 2) Investigate the metabolic protein shifts due to aging and post thyroid hormone treatment. She also collaborates with other PIs in the department. The environment is conducive to such collaborations and offers opportunities to expand on research initiatives. Dr. Ledee is presently working on the completion of 2 first authorship papers. She is responsible for training all of the medical fellows and undergraduates that rotate through the lab. Dr. Ledee has been in Dr. Portman's lab for 3 years and has been indoctrinated into a new field of research. It is her intent to embark upon an independent research career in cardiac metabolism, and Seattle Children's Research Institute resources are excellent. In addition to the incredibly knowledgeable scientist the physical place is well equipped for the type of molecular experiments Dr. Ledee has envisioned. The research project Dr. Ledee has proposed investigates thyroid receptors functional changes in the aged heart. The aged heart is observed to undergo structural, metabolic and molecular changes; and with an ever increasing older population damaging cardiovascular events will also increase. Previous experiments in the lab observed that thyroid hormone treatment could reverse the metabolic shift in the aged heart without a change in thyroid receptor expression. Based on this result Dr. Ledee proposed to examine potential epigenetic and post-translational modification regulation of the thyroid receptors. Additionally, in prior experiments she identified several proteins that interact with TRB1, which have not been previously reported. She proposes to examine the mechanisms of the interaction and potential functional role. Her 3rd aim focuses on identifying proteins that have altered expression in response to thyroid hormone treatment in the aged heart as a method to understand the molecular changes that occur with aging. In conclusion, I believe my proposal addresses a very serious problem in human health, cardiovascular aging. The K01 grant offers the means to pursue the goal of being an independent principle investigator. (End of Abstract)