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.

这是一项经过良好注重患者的开发奖的修订申请，以使Wael N. Jarjour博士能够将他的75％的时间投入到包括教学课程和实验室调查的计划中，以使他能够获得生物统计学，人类调查，研究，研究设计和实验研究的培训。该计划将促进他的职业发展成为独立的临床研究者。该计划包括涉及基本统计数据，高级统计建模，临床研究中的基本方法和临床研究道德行为的强烈课程的教学课程。 有人建议他将由Margaret Shupnik博士对分子内分泌学培训，他将担任主要导师，并由Shu Man Fu博士作为他的同事在细胞免疫学方面进行培训。 已经成立了一个委员会，以监控他的进步和内科部主席的承诺，要求有75％的保护时间来实现该奖项概述的目标。 已经设计了一项研究计划，该计划解决了有关系统性红斑狼疮（SLE）性别偏见（SLE）的一个重要问题，该问题主要影响女性，主要影响肾脏是主要的目标器官之一。该研究计划已被修订，以考虑审稿人的关注。 它涉及雌激素受体（ER）在SLE发病机理中的作用。 这种疾病在生殖生活中主要影响女性。 还证明，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SLE（一种系统的自身免疫性疾病）中的作用是合乎逻辑的。 初步数据表明，来自正常患者和SLE患者的淋巴细胞α和雌激素受体表达之间的明显差异。提出了四个具体目的：1）检查与健康对照组相比，在SLE患者的循环T细胞中，ERALPHA和ERBETA的蛋白质和mRNA表达； 2）确定sLE患者和对照组的T淋巴细胞中ER激活是否有所不同； 3）确定SLE患者T细胞和某些正常对照群体T细胞的敏感性是否改变是由于ODF蛋白调节ER激活的影响。 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的所需培训，并补充教学课程。通过教学课程和实验室调查，Jarjour博士将达到他的目标，使其成为一个独立的临床研究者，具有研究免疫学基础人类疾病机制的能力，并基于对这些机制的理解来设计新的治疗方法。