Dynamics of the Human Thyroid: Towards Clinical Applications

摘要甲状腺是内分泌系统中最大的腺体，分泌调节体内稳态功能、促进正常生长发育的激素。近年来，在识别甲状腺内的化学信号通路方面取得了很大进展。基于最近分子水平的发现和临床观察，这个团队设计了一个详细的甲状腺计算模型。在该模型的发展和证实的推动下，本研究的主要目标是了解甲状腺的基本动态，并将这种理解转化为治疗甲状腺功能障碍的治疗方案。建议研究的例子包括：1)了解甲状腺肿大（甲状腺肿）的动态；2)分析药物和环境污染物对甲状腺激素分泌的影响；3)改进放射性碘治疗graves病。这项工作的智力价值集中在计算建模，动力系统分析和临床经验的协调上。拟议研究的更广泛影响具有短期和长期影响：(i)提高诊断能力（早期干预），（ii）改进治疗方案（格雷夫斯病和激素替代），以及（iii）加强药物测试/筛选（模拟、增强、减弱或阻断激素作用）。

AbstractThe thyroid, the largest gland in the endocrine system, secretes hormones that regulate homeostatic functions within the body and promote normal growth and development. In recent years, great strides have been made in identifying chemical signal pathways within the thyroid. Based upon recent molecular-level discoveries and clinical observations, this team has engineered a detailed computational model of the thyroid gland. Motivated by this model's development and confirmation, the main goal of the proposed research is to understand the thyroid's fundamental dynamics and to translate this understanding into therapeutic protocols for treating thyroid dysfunction. Examples of the proposed research include: 1) Understanding the dynamic of thyroid enlargement (goiter), 2) Analyzing the effects of drugs and environmental contaminants on thyroid hormone secretion, and 3) Improving radioactive iodine treatment of Grave's disease. The intellectual merit of this work is centered upon coordination of computational modeling, dynamical systems analysis, and clinical experience. The broader impact of the proposed research has short and long term implications: (i) improving diagnosis power (early intervention), (ii) improving treatment protocols (Grave's disease and hormone replacement), and (iii) enabling enhanced testing/screening of pharmaceuticals (mimic, enhance, diminish or block hormone actions).