MENTORING IN RESEARCH ON ENDOMETRIOSIS

Ana a . Murphy博士是埃默里大学医学院妇产科教授，生殖内分泌和不孕症部门主任。Murphy博士在埃默里大学发起、设计并实施了生殖内分泌学和不孕症奖学金，该奖学金目前已获得美国妇产科委员会的批准。她于1997年成为首任董事，并于1998年接受了她的第一位研究员。目标是帮助学员出版和认可，并实现独立的研究支持。成功的导师必须指导学生提出具有独创性和价值的假设，提供测试假设的实验工具，帮助学生确定有价值的研究领域，并保持专注。用于培训学员的研究方向将是子宫内膜异位症和平滑肌瘤的病理生理学研究。她一直致力于指导和培训以患者为导向的研究。墨菲博士的主要研究重点是子宫内膜异位症，其病理生理学以及手术/药物治疗。我们的假设侧重于氧化应激作为刺激剂，导致腹膜液改变和巨噬细胞激活，介导这些患者的不孕和疼痛。在第一年，我们积累了大量的基础和临床数据，以支持我们的假设，即子宫内膜异位症患者存在显著的氧化应激。Aim 1的招募工作已经完成，数据正在分析中。目标2、3的招募正在进行中。我们用RU486作为生物探针，研究了低剂量在体内对子宫内膜和平滑肌瘤的调节作用。初步资料显示，平滑肌瘤和肌层免疫染色为糖苷。反过来，糖苷已被证明可以降低自然杀伤细胞（NK细胞）的活性，这种活性在患有平滑肌瘤的女性中也会降低。我们推测RU486具有通过其抗氧化活性介导的直接抗增殖作用和通过降低糖苷水平介导的间接免疫调节作用。糖苷可提高NK细胞活性，从而抑制肿瘤生长。

Dr. Ana A. Murphy is a professor in Gynecology and Obstetrics and Director of the Division of Reproductive Endocrinology and Infertility at Emory University School of Medicine. Dr. Murphy initiated, designed and implemented the Reproductive Endocrinology and Infertility Fellowship at Emory University that is currently approved by the American board of Obstetrics and Gynecology, Inc. Dr. Murphy became first Director in1997 and accepted her first fellow in 1998. The goal is to help the mentee became published and recognized and to achieve independent research support. The successful mentor must provide instruction on development of hypotheses that are original and worthwhile, the experimental tools to test the hypotheses, help the mentee identify a worthwhile field of investigation, and to remain focused. The line of research used to train the mentees will be the study of the pathophysiology of endometriosis and leiomyoma. She has demonstrated continued commitment to mentoring and training in patient-orientated research. The main focus of Dr. Murphy's research has been endometriosis, its pathophysiology as well as its surgical/medical treatment. Our hypothesis focuses on oxidative stress as the inciting agent that results in peritoneal fluid changes and activation of macrophages that mediate the infertility and pain seen in these patients. In the first year we have accumulated significant basic and clinical data in support of our hypothesis that a significant oxidative stress occurs in women with endometriosis. Recruitment for Aim 1 is complete and the data is being analyzed. Recruitment is underway for Aims 2,3. We have used RU486 as a biologic probe to study the in vivo regulation of endometrium and leiomyoma seen with low dose, in vivo. Preliminary data, has shown that leiomyoma and myometrium immunostain for glycodelin. In turn, glycodelin has been shown to decrease natural killer cell (NK cell) activity which is also decreased in women with leiomyoma. We hypothesize that RU486 has direct antiproliferative effect mediated by its antioxidant activity and an indirect immunomodulatory effect by decreasing glycodelin levels. Glycodelin may increase NK cell activity thus decreasing tumor growth.