The Massachusetts General Hospital Harvard Center for Reproductive Medicine

马萨诸塞州总医院哈佛生殖医学中心

• 批准号: 10463543
• 负责人: Stephanie Beth Seminara
• 金额: $ 155.04万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-10 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10463543
• 关键词: Address; Affect; Age; Architecture; Biological; Biological Factors; Biological Process; Boston; Brain; Cells; Center for Translational Science Activities; Child; Clinical; Clinical Research; Clinical Treatment; Collection; Communication; Communities; Computational Biology; Counseling; Couples; Creativeness; DNA; Data Analytics; Denmark; Diagnosis; Disease; Education and Outreach; Endocrinology; Estonia; Ethnic group; Faculty; Family; Fertility; Financial Hardship; Finland; Fostering; Future; GNRH1 gene; General Hospitals; Genes; Genetic; Genetic Engineering; Genomics; Genotype; Goals; Gonadal structure; Group Meetings; Gynecology; Health; Hospitals; Human; Human Development; Human Engineering; Hypogonadism; Individual; Infertility; Information Dissemination; Institution; Interdisciplinary Study; International; Investigation; Knowledge; Lead; Leadership; Link; Longitudinal Studies; Massachusetts; Mendelian randomization; Mentors; Mentorship; Methodology; Methods; Morbidity - disease rate; Mutation; National Institute of Child Health and Human Development; Parents; Pathway interactions; Patients; Pediatric Surgical Procedures; Penetrance; Phenotype; Physiological; Population; Population Genetics; Positioning Attribute; Prevention; Provider; Public Health; Rare Diseases; Reproduction; Reproductive Biology; Reproductive Health; Reproductive Medicine; Research; Research Personnel; Research Project Grants; Resources; Role; Sampling; Scientist; Services; Strategic vision; Technology; Therapeutic; Thinking; Time; Training; Urology; Validation; Work; biobank; clinical care; clinical investigation; cohort; community engagement; computerized tools; cost; design; evidence base; flexibility; functional genomics; gene discovery; gene function; genetic architecture; genome editing; genome wide association study; genomic variation; gonad development; human disease; improved; infertility treatment; innovation; lens; literacy; member; mortality; multi-ethnic; neuron development; next generation; next generation sequencing; outreach; phenome; phenomics; population based; psychologic; reproductive; research and development; sex; skills; sustainable resource; targeted treatment; trait; transcriptomics; translational scientist; web site

PROJECT ABSTRACT Infertility affects up to 13% of reproductive age couples across the globe but the underlying mechanistic basis of infertility and the role of infertility as an overall marker of general health is unclear. These knowledge gaps hinder the diagnosis, treatment and prevention of infertility leading to physical, psychological and financial burden to couples with infertility. To address these challenges, The Massachusetts General Hospital Harvard Center for Reproductive Medicine has assembled an integrative team of investigators with expertise in reproductive medicine, genomics, population genetics and genetic literacy who will conduct clinical translational investigation in humans with infertility: Aim 1: To elucidate the genetic and phenomic architecture of infertility through the lens of specific rare diseases and common traits; Aim 2: To catalyze a collaborative think-tank focused on reducing the suffering and costs of infertility, in a manner that is outward looking, forward thinking and integrates global perspectives; Aim 3: To nucleate a vibrant hub for outreach, training and community engagement that brings the scientific team closer to the patients they serve, the trainees they want to mentor, and the larger community of scientists and clinicians who are invested in reducing the burdens caused by infertility. These aims will be achieved using two Clinical Research projects which will be supported by a Genomics and Functional Core, Outreach Core and Administrative Core. Project 1 will perform next-generation sequencing and targeted genotype-driven phenotyping studies in clinical cohorts enriched for genetically driven infertility from admixed and consanguineous populations characterized by both hypogonadotropic and hypergonadotropic hypogonadism in both sexes. Project 2 will bring together >1,800,000 multi-ethnic population biobank samples to perform genome-wide association studies, phenome-wide association studies, and Mendelian randomization studies to implicate key biologic pathways determining fertility and synthesize the genetic results across infertility and related traits to characterize the effects of the identified genes and pathways on reproductive health and overall morbidity. The Genomics and Functional Core will provide genomic technologies, data analytics, computational and statistical support, and will generate genetically engineered human induced pluripotent cells for validation of Project 1 & 2 genetic discoveries. The Outreach Core will buoy Project 1 & 2 activities by engaging key stakeholders through patient group meetings, creating clinician-facing materials to enable communication of genetic results and launch a website inspired by design-thinking for broad dissemination to patients, families and clinicians. The Administrative Core will advance the Center’s scientific goals by providing timely support to foster engagement and communication between investigators, patients, research trainees and the broader academic community. Through these interdigitating activities, the Center will train the next generation of reproductive biologists and the results emanating from its activities will help inform clinical care and alleviate the suffering of patients with infertility.

项目摘要 不孕症影响多达13％的全球生殖年龄夫妇，但基础机械基础 不育和不育作为一般健康的总体标志的作用尚不清楚。这些知识差距阻碍 不孕的诊断，治疗和预防导致身体，心理和金融伯恩的诊断和预防 夫妻有不育。为了应对这些挑战，马萨诸塞州哈佛大学综合医院 生殖医学已经组建了一个综合研究人员，并具有生殖专家 医学，基因组学，人群遗传学和遗传学素养，他们将进行临床翻译研究 在具有不育的人：目标1：通过镜头阐明不育的遗传和现象结构 特定的稀有疾病和常见特征；目标2：催化专注于减少的协作智囊团 不育的痛苦和成本，以一种外向，向前思考和整合全球的方式 观点；目标3：核一个充满活力的枢纽，以进行外展，培训和社区参与，这带来了 科学团队更接近他们服务的患者，他们想精神上的学员以及更大的社区 投资用于减少不孕症造成的伯内斯的科学家和临床医生。这些目标将是 使用两个临床研究项目实现了，这些项目将由基因组学和功能核心支持， 外展核心和行政核心。项目1将执行下一代测序并针对性 基因型驱动的表型研究在临床队列中富含遗传驱动的不孕症的临床群体研究。 以及以降压和高产量性的直接种群为特征 性别中的性腺功能不全。项目2将汇集> 1,800,000个多民族人口生物库样本 进行全基因组关联研究，全球范围的关联研究和孟德尔随机化 实施关键生物学途径的研究，以决定生育能力并综合不孕症的遗传结果 和相关特征以表征已鉴定的基因和途径对复制健康的影响 总体发病率。基因组学和功能核心将提供基因组技术，数据分析， 计算和统计支持，并将生成基因设计的人类诱导的多能细胞 用于验证项目1和2遗传发现。外展核心将审理1和2项目的活动 通过患者小组会议吸引关键利益相关者，创建临床材料以启用 遗传结果的沟通并启动了一个受设计思维启发的网站，以进行广泛的传播 患者，家庭和临床医生。行政核心将通过提供中心的科学目标来推进中心的科学目标 及时支持调查人员，患者，研究培训和 更广泛的学术界。通过这些互合活动，中心将训练下一个 生殖生物学家的产生以及其活动产生的结果将有助于临床护理 并减轻不育患者的痛苦。