Studies of Estrogen Receptors in Autoimmunity

自身免疫中雌激素受体的研究

• 批准号: 6471700
• 负责人: WAEL N JARJOUR
• 金额: $ 12.76万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6471700
• 关键词: T lymphocyte; estrogen receptors; estrogens; female; hormone regulation /control mechanism; human subject; immunomodulators; immunopathology chemotherapy; patient oriented research; receptor binding; receptor expression; systemic lupus erythematosus

This is an amended application for a mentored patient-oriented development award to enable Dr.Wael N. Jarjour to devote 75% of his time for five years to a program that includes didactic coursework and laboratory investigatiion to enable him to obtain training in biostatistics, human investigation, research design and experimental investigation. This program will facilitate his career development to be an independent clinical investigator. This program consists of didactic coursework involving basic statistics, advanced statistical modeling, fundamental methodologies in clinical investigation, and a intense course in ethical conduct of clinical investigation. It is proposed that he will be trained in molecular endocrinology by Dr.Margaret Shupnik who will serve as primary mentor, and in cellular immunology by Dr. Shu Man Fu as his co-mentor. A committee has been set up to monitor his progress and the commitment from the Chair of the Department of Internal Medicine to have 75% protected time to achieve the goals as outlined for this award. A research program has been devised which addresses an important issue regarding gender bias in systemic lupus erythematosus (SLE) which affects females predominately and the kidney as one of the major target organs. The research plan has been revised taking the Reviewers' concerns in to consideration. It deals with the role of estrogen receptors (ER) in the pathogenesis of SLE. This disease affects predominately females in their reproductive life. It has also been demonstrated that female hormones such as estrogen have profound effects on the immune system. Thus, it is logical to study the role of estrogen receptors in SLE, a protyppic disease of systematic autoimmunity. Preliminary data have suggested marked differences between alpha nd beta estrogen receptor expression by lymphocytes from normals and SLE patients. Four specific aims are proposes: 1) to examine the protein and mRNA expression of ERalpha and Erbeta in circulating T cells of patients with SLE in comparison with healthy controls; 2) to determine if ER activation differs in T lymphocytes from SLE patients and controls; and 3) to determine whether altered sensitivity of T cells from SLE patients and certain normal control populations is due to the effects odf protein which regulate ER activty. This research plan will provide Dr. Jarjour the needed training in experimental design and techniques, data analyses, and manuscript preparation as well as to complement the didactic coursework. Through both didactic coursework and laboratory investigation, Dr. Jarjour will attain his goals to develop into an independent clinical investigator with ability to study mechanisms of human diseases of immunological basis and to devise novel therapeutic approaches based on the understanding of these mechanisms.

这是对以患者为导向的发展奖的修改申请，使 Wael N. Jarjour 博士能够在五年内将 75% 的时间投入到一个项目中，其中包括教学课程和实验室研究，使他能够获得生物统计学、人体调查、研究设计和实验调查方面的培训。该计划将促进他的职业发展，成为一名独立的临床研究者。该项目包括教学课程，涉及基础统计学、高级统计模型、临床研究的基本方法以及临床研究道德行为的强化课程。 拟由Margaret Shupnik博士担任主要导师进行分子内分泌学培训，并由Shu Man Fu博士作为副导师进行细胞免疫学培训。 已经成立了一个委员会来监督他的进展以及内科系主任的承诺，即有 75% 的保护时间来实现该奖项概述的目标。 一项研究计划旨在解决系统性红斑狼疮 (SLE) 中性别偏见的重要问题，该病主要影响女性，肾脏是主要靶器官之一。考虑到审稿人的担忧，对研究计划进行了修订。 它涉及雌激素受体 (ER) 在 SLE 发病机制中的作用。 这种疾病主要影响女性的生殖生活。 研究还表明，雌激素等女性激素对免疫系统具有深远的影响。 因此，研究雌激素受体在系统性红斑狼疮（一种系统性自身免疫性疾病的典型疾病）中的作用是合乎逻辑的。 初步数据表明正常人和 SLE 患者淋巴细胞的 α 和 β 雌激素受体表达存在显着差异。提出了四个具体目标：1）与健康对照相比，检查 SLE 患者循环 T 细胞中 ERα 和 Erbeta 的蛋白质和 mRNA 表达； 2) 确定 SLE 患者和对照的 T 淋巴细胞中 ER 激活是否存在差异； 3) 确定 SLE 患者和某些正常对照群体 T 细胞敏感性的改变是否是由于调节 ER 活性的 odf 蛋白的影响所致。 该研究计划将为 Jarjour 博士提供实验设计和技术、数据分析和手稿准备方面所需的培训，并补充教学课程。通过教学课程和实验室研究，Jarjour 博士将实现他的目标，即发展成为一名独立的临床研究者，有能力研究人类疾病免疫学基础的机制，并在了解这些机制的基础上设计新的治疗方法。