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

加州大学旧金山分校斯坦福子宫内膜异位症发现、创新、培训和社区参与中心

• 批准号: 10308246
• 负责人: LINDA C GIUDICE
• 金额: $ 144.78万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10308246
• 关键词: Adaptive Immune System; Address; Affect; Age; Animal Model; Area; Aromatase Inhibitors; Autoimmune; Awareness; Biological Markers; Cardiovascular Diseases; Cells; Characteristics; Chronic; Cicatrix; Classification; Clinical; Clinical Data; Collaborations; Communities; Community Outreach; Complex; Computational Science; Contraceptive Agents; Coupled; DNA Library; Data; Databases; Diagnosis; Diagnostic; Discipline; Disease; Disease Management; Disease stratification; Dysmenorrhea; Ecology; Education; Education and Outreach; Endometrial; Endometrium; Environment; Estradiol; Estrogens; Etiology; Excision; Fatigue; Fertility; Fostering; Functional disorder; GNRH1 gene; Genetic; Genomics; Goals; Health; Health Expenditures; Health Professional; Heterogeneity; Hormonal; Human; Immunologics; Immunology; Incidence; Infectious Agent; Infertility; Inflammation; Inflammatory; Inflammatory Response; Informatics; Institution; Lesion; Life; Machine Learning; Malignant - descriptor; Malignant Neoplasms; Medical; Mental Depression; Mentors; Mentorship; Multiomic Data; Non-Malignant; Non-Steroidal Anti-Inflammatory Agents; Operative Surgical Procedures; Organ; Outcome; Pain; Pain management; Pathogenesis; Pathology; Patient-Focused Outcomes; Pelvic Pain; Pelvis; Peritoneum; Personal Satisfaction; Pharmaceutical Preparations; Phenotype; Positioning Attribute; Pregnancy Outcome; Proteomics; Quality of life; Recurrence; Research; Research Personnel; Research Project Grants; Resolution; Resources; Risk; Science; Scientist; Severities; Steroids; Students; Surgeon; Symptoms; Systems Biology; Technology; Teenagers; Tissue Banks; Tissues; Training; Transcend; United States National Institutes of Health; Universities; Uterus; Validation; Viral; Woman; Women' s Health; analog; biological specimen archives; career; career development; chronic pelvic pain; clinical care; clinical phenotype; clinically relevant; community engagement; comorbidity; diagnostic biomarker; disease classification; disease diagnosis; disease heterogeneity; disease phenotype; diversity and inclusion; drug discovery; drug repurposing; economic impact; endometriosis; girls; health disparity; health economics; human tissue; improved; innovation; interdisciplinary collaboration; member; metabolomics; minimally invasive; multidisciplinary; multiple omics; next generation; novel; novel therapeutic intervention; novel therapeutics; pain relief; pain symptom; persistent organic pollutants; phenotypic data; precision medicine; programs; reproductive; response; response biomarker; side effect; student training; systemic inflammatory response; technological innovation; therapeutic biomarker; transcriptomics; treatment response

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.

摘要 - 总体 子宫内膜异位症是一种慢性、使人衰弱的雌激素依赖性疾病，其中类似于子宫内膜的组织 （子宫内膜）主要存在于盆腔组织和器官中，引起炎症反应、疤痕、 骨盆疼痛和不孕。它影响着数百万育龄妇女并严重影响生活质量和 职业生涯，并且在美国每年产生约 $69B 的巨大健康经济影响，而其病因是 先天性和适应性免疫系统的不确定的、严重的功能障碍与低效病变有关 清除以及盆腔和全身炎症。子宫内膜异位症病变和疾病的异质性 表型反映在不同的疼痛症状表现、不可预测的生育潜力、不确定 疾病病理生理学，以及对药物治疗、症状和疾病复发的不可预测的反应 手术切除后以及合并症的风险。子宫内膜异位症的临床分类不适应 疾病表现的异质性，因此缺乏对相关疼痛症状的有效治疗。 在此，我们的加州大学旧金山分校斯坦福子宫内膜异位症发现、创新、培训和社区中心 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 合作与科技创新，整合多组学数据剖析子宫内膜异位症 疾病机制，识别表型和环境疾病特征，开发准确的疾病 分层和诊断，并确定新的和重新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 个独立的互动项目和 2 个核心组成，专注于 子宫内膜异位症精准医学的中心主题。项目1将重点关注基础免疫学 子宫内膜异位症发病机制和病理生理学机制。项目 2 将解决开发多 组学疾病分类将为诊断策略提供信息，项目 3 将利用现有的和新的 生成大规模组学数据来识别和验证新的治疗干预措施。我们长期坚持的人类 子宫内膜组织和 DNA 银行以及 REDCap 数据库以及我们合作网络的持续累积 外科医生将成为该中心项目的主要资源。该中心将设有一个行政核心和一个 教育和社区外展核心将使湾区的学生参与我们的研究项目 赋予我们社区中的妇女权力并解决与子宫内膜异位症相关的健康差异。达到 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由多学科研究人员组成的团队，其中许多人 其中包括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 所有人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手之间的合作，培训下一代并建立伙伴关系 与我们社区的合作是子宫内膜异位症中心取得成果和影响的关键。