Thyrocytes Express Inflammatory Mediators

描述（由申请人提供）：对自身免疫性甲状腺疾病、桥本甲状腺炎和格雷夫斯病（GD）的理解仍然很肤浅，目前的治疗以甲状腺功能亢进为导向。 负责自身免疫性甲状腺的淋巴细胞浸润和炎症特征的介质尚未确定。 本项目的长期目标是研究甲状腺上皮细胞在炎症反应中的作用。在这里，我们提出的实验设计1）调查甲状腺炎症的发病机制2）确定潜在的治疗靶点中断这些过程和3）确定自身免疫性甲状腺疾病活动的临床标志物。细胞免疫学，蛋白质化学和分子生物学技术将被用来检查甲状腺细胞表达的免疫调节分子在体外和原位。我们建议在一项为期48个月的Graves病患者前瞻性研究中，测量血清炎症介质水平，并试图将其血清水平与疾病活动性联系起来。 候选人和导师密切合作超过3年。这种关系导致大量的生产和辅助初步数据的产生。在研究职业发展奖的支持下，继续指导和一般临床研究中心的可用性，候选人将能够进一步调查他的发现并回答出现的临床相关问题。在职业发展期间，候选人还将完成分子生物学和转化研究的研究生水平课程。 候选人将发展科学知识基础，解决问题的能力和技术技能，使他能够发展成为独立的医生/科学家。

DESCRIPTION (provided by applicant): The understanding of autoimmune thyroid diseases, Hashimoto's thyroiditis and Graves disease (GD), remains superficial and current treatment is symptom-oriented. The mediators responsible for the lymphocytic infiltration and inflammation characteristic of autoimmune thyroid glands have not been identified. The long-term objective of this project is to investigate the role of thyroid epithelial cells in the inflammatory response. Here, we propose experiments designed to 1) investigate the pathogenesis of thyroid inflammation 2) identify potential therapeutic targets for interrupting these processes and 3) identify clinical markers of autoimmune thyroid disease activity. Cellular immunology, protein chemistry and molecular biology techniques will be utilized to examine thyrocyte expression of immunomodulatory molecules in vitro and in situ. We propose to measure serum levels of inflammatory mediators and attempt to correlate their serum levels with disease activity in a 48-month prospective study of patients with Graves' disease. The candidate and mentor have worked closely for over 3 years. This relationship has led to significant production and the generation of supporting preliminary data. With the support of a research career development award, continued mentoring and the availability of a General Clinical Research Center, the candidate will be able to further investigate his findings and answer the clinically relevant questions that have arisen. During the career development period, the candidate will also complete graduate level coursework in molecular biology and translational investigation. The candidate will develop the scientific knowledge base, problem solving abilities, and technical skills which will allow him to develop into a independent physician/scientiist.