Studies of Estrogen Receptors in Autoimmunity

自身免疫中雌激素受体的研究

• 批准号: 6623998
• 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/6623998
• 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.

这是一个修改后的申请辅导病人为导向的发展奖，使博士瓦埃勒N。Jarjour将在五年内将75%的时间投入到一个包括教学课程和实验室调查的项目中，使他能够获得生物统计学，人类调查，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。该计划包括教学课程，涉及基本统计，高级统计建模，临床调查的基本方法，以及临床调查伦理行为的密集课程。 建议他接受Margaret Shupnik博士的分子内分泌学培训，Margaret Shupnik博士将担任主要导师，Shu Man Fu博士将担任其共同导师。 已经成立了一个委员会来监测他的进展情况，以及内科系主任承诺有75%的保护时间来实现该奖项所概述的目标。 一项研究计划已经制定，解决了一个重要的问题，性别偏见的系统性红斑狼疮（SLE），影响女性为主，肾脏作为一个主要的靶器官。考虑到审查员的关切，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。 这种疾病主要影响处于生育期的女性。 研究还表明，雌激素等女性激素对免疫系统有深远的影响。 因此，研究雌激素受体在系统性自身免疫性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α和β雌激素受体表达有显著差异。本研究的主要目的是：1）检测SLE患者外周血T淋巴细胞ER α和ER β的蛋白和mRNA表达，并与健康对照组进行比较; 2）确定SLE患者和健康对照组T淋巴细胞ER活化是否存在差异;和3）为了确定来自SLE患者和某些正常对照群体的T细胞的敏感性改变是否是由于odf蛋白的作用，调节ER活性。 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的必要培训，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，发展成为一名独立的临床研究者，能够研究免疫学基础上的人类疾病机制，并根据对这些机制的理解设计新的治疗方法。