UCSF Stanford Endometriosis Center for Discovery, Innovation, Training and Community Engagement

摘要-总体 子宫内膜异位症是一种慢性的、使人衰弱的雌激素依赖性疾病， （子宫内膜）主要在盆腔组织和器官上发现，在那里它引起炎症反应，瘢痕形成， 盆腔疼痛和不孕症它影响到数百万育龄妇女，严重影响生活质量， 职业生涯，并有一个巨大的健康经济影响约690亿美元，每年在美国，而其病因是 先天性和适应性免疫系统的不确定的、深刻的功能障碍与无效的损伤有关 清除和盆腔及全身炎症。子宫内膜异位症病变和疾病的异质性 表型反映在可变的疼痛症状表现，不可预测的生育潜力，不确定的 疾病病理生理学，以及对药物治疗的不可预测的反应，症状和疾病复发 以及合并症的风险。子宫内膜异位症的临床分类不适应于 缺乏疾病表达的异质性，因此缺乏对相关疼痛症状的有效治疗。 在此，我们的UCSF斯坦福大学子宫内膜异位症中心的发现，创新，培训和社区 Engagement（“ENACT”）提出了一种全面的系统生物学和精准医学方法， 子宫内膜异位症我们建议通过跨学科研究子宫内膜异位症未满足的需求和挑战 合作和科技创新，整合多组学数据来解剖子宫内膜异位症 疾病机制，识别表型和环境疾病特征， 分层和诊断，并确定新的和再利用的药物类别，以改善疼痛症状。到 为了实现这些目标，我们的中心由3个独立和互动的项目和2个核心组成，重点是 子宫内膜异位症精准医学的中心主题。项目1将侧重于基础免疫学 子宫内膜异位症的发病机制和病理生理学。项目2将致力于开发一个多- 将告知诊断策略的组学疾病分类，项目3将利用现有和新的 产生了大规模的组学数据，以确定和验证新的治疗干预措施。长期以来， 子宫内膜组织和DNA库和REDCap数据库以及与我们合作网络的持续累积 外科医生将是本中心项目的主要资源。该中心将有一个行政核心和一个 教育和社区外展核心，将吸引来自湾区的学生参与我们的研究计划 并赋予我们社区的妇女权力，解决与子宫内膜异位症相关的健康差距。实现 为了实现这些目标，我们在加州大学旧金山分校和斯坦福大学组建了一个多学科的调查小组， 他们是子宫内膜异位症研究的新手，以及教育工作者，学员和社区代表， 都致力于改善患有子宫内膜异位症的妇女和少女的生活。融合多学科， 促进子宫内膜异位症新患者之间的合作，培训下一代并建立伙伴关系 与我们的社区是我们的子宫内膜异位症中心的结果和影响的关键。

ABSTRACT - OVERALL Endometriosis is a chronic, debilitating estrogen-dependent disease wherein tissue similar to the uterine lining (endometrium) is found mainly on pelvic tissues and organs where it causes an inflammatory response, scarring, pelvic pain, and infertility. It affects millions of reproductive age women and severely impacts quality of life and professional life, and has a huge health economic impact of about $69B annually in the U.S. While its etiology is uncertain, profound dysfunction of the innate and adaptive immune systems is associated with inefficient lesion clearance and pelvic and systemic inflammation. The heterogeneity of endometriosis lesions and disease phenotypes is reflected in variable pain symptom presentations, unpredictable fertility potential, uncertain disease pathophysiology, and unpredictable responses to medical therapies, symptom and disease recurrence after surgical resection, and risks for co-morbidities. Clinical classifications of endometriosis are maladapted to the heterogeneity of disease expression, and thus efficient treatments for associated pain symptoms are lacking. Herein, our UCSF Stanford Endometriosis Center for Discovery, Innovation, Training and Community Engagement (“ENACT”) proposes a comprehensive systems biology and precision medicine approach to endometriosis. We propose to study endometriosis unmet needs and challenges through transdisciplinary collaboration and scientific and technologic innovations, integrating multi-omics data to dissect endometriosis disease mechanisms, identify phenotypic and environmental disease signatures, develop accurate disease stratification and diagnosis, and identify novel and repurposed drug classes to ameliorate pain symptoms. To achieve these goals, our Center is comprised of 3 independent and interactive projects and 2 Cores, focused on the central theme of Endometriosis Precision Medicine. Project 1 will focus on underlying immunological mechanisms in endometriosis pathogenesis and pathophysiology. Project 2 will address developing a multi- omic disease classification that will inform diagnostic strategies, and Project 3 will leverage existing and newly generated large-scale omic data to identify and validate new therapeutic interventions. Our long-standing Human Endometrial Tissue and DNA Bank and REDCap database and ongoing accruals with our collaborating network of surgeons will be a major resource for this Center's project. The Center will have an Administrative Core and an Education and Community Outreach Core that will engage students from the Bay Area in our research programs and empower women in our community and address health disparities associated with endometriosis. To achieve these goals, we have assembled a multi-disciplinary team of investigators at UCSF and Stanford University, many of whom are new to endometriosis research, as well as educators, trainees, and community representatives who are all committed to improve the lives of women and teen girls with endometriosis. Integrating multiple disciplines, fostering collaborations among those who are new to endometriosis, training the next generation and partnering with our community are key to the outcomes and impact of our Endometriosis Center.