Paxillin and Androgens in the Regulation of Ovarian Follicle Development

桩蛋白和雄激素在卵巢卵泡发育调节中的作用

基本信息

  • 批准号:
    10688086
  • 负责人:
  • 金额:
    $ 15.87万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-09-01 至 2025-08-31
  • 项目状态:
    未结题

项目摘要

1 Project Summary / Abstract 2 This career development project will provide a path for a highly qualified candidate with a combined MD/PhD 3 degree into a career as an independent investigator in reproductive science. Female infertility due to disorders 4 of androgen excess or insufficiency is a growing problem in the U.S. and worldwide with high mental and financial 5 costs. Androgen imbalance is implicated in polycystic ovary syndrome (PCOS) and diminished ovarian reserve 6 (DOR); however, while the phenotypic effects of androgen activity in the ovary are significant, little is known 7 about the underlying molecular pathways. This proposal aims to elucidate the mechanisms of androgen actions 8 in ovarian follicle growth and atresia, which are disordered in PCOS and DOR. The research direction stems 9 from the recent finding by the candidate that the androgen-regulated mRNA transcriptome in ovarian granulosa 10 cells is surprisingly small, and focuses on non-coding RNA regulation by androgens in granulosa cells. The 11 proposal also builds on prior studies of paxillin as a mediator of androgen signaling in prostate cancer. The role 12 of paxillin as a regulator of the androgen receptor expression is assessed for the first time in granulosa cells in 13 this proposal. The effects of paxillin loss in granulosa cells on follicular development and fertility will be examined 14 in a granulosa cell-specific knockout mouse model. The molecular mechanisms involving microRNA regulation 15 by androgens in granulosa cells will be studied in cultured mouse and human cells. The hypothesis is that 16 androgen effects in granulosa cells are mediated in large part by microRNAs, and are enhanced by paxillin. The 17 project has the potential to suggest novel therapeutic avenues for PCOS, a disease with sub-optimal 18 management options. The training plan capitalizes on the applicant’s strong research background and long- 19 standing interest in female fertility. She aims to build on her technical skills, develop as a leader and a member 20 of the scientific community, and transition to independence in research. The mentor is a physician-scientist who 21 is a world expert in paxillin and androgen signaling, mouse genetics and ovarian biology with a long track record 22 of mentoring successful trainees. The training will take place in a highly collaborative environment where 23 expertise in reproductive research techniques is abundant. The applicant has assembled an advisory committee 24 comprised of world experts in ovarian biology, paxillin, steroid signaling, and microRNA sequencing. She will 25 take advantage of University-sponsored courses in translational research methods, leadership and professional 26 development, as well as research seminars, national meetings and one-on-one instruction. At the end of this 27 project, she plans to write several first-author publications, run a lab independently, mentor a graduate student 28 and apply for an R-01 grant.
1项目概要/摘要 2这个职业发展项目将为一个高素质的候选人提供一条道路, 3度进入职业生涯作为一个独立的调查员在生殖科学。疾病导致的女性不孕症 雄激素过多或不足在美国和全世界都是一个日益严重的问题, 5成本。雄激素失衡与多囊卵巢综合征(PCOS)和卵巢储备功能下降有关 6(DOR);然而,虽然卵巢雄激素活性的表型效应是显着的,但知之甚少 7关于潜在的分子途径。该建议旨在阐明雄激素作用的机制 8例卵泡发育和闭锁,PCOS和DOR患者卵泡发育和闭锁紊乱。研究方向源于 9从候选人最近的发现,雄激素调节的mRNA转录组在卵巢颗粒细胞 10细胞是令人惊讶的小,并集中在非编码RNA的调节雄激素在颗粒细胞。的 11提案还建立在桩蛋白作为前列腺癌中雄激素信号传导的介质的先前研究的基础上。的作用 12的桩蛋白作为雄激素受体表达的调节剂首次在卵巢颗粒细胞中进行评估, 13、这个建议将检测颗粒细胞中桩蛋白缺失对卵泡发育和生育力的影响 14在颗粒细胞特异性敲除小鼠模型中。microRNA调控的分子机制 将在培养的小鼠和人细胞中研究雄激素在颗粒细胞中的作用。前提是 16颗粒细胞中的雄激素效应在很大程度上由microRNA介导,并由桩蛋白增强。的 17项目有可能为PCOS提出新的治疗途径,PCOS是一种次优的疾病, 18个管理选项。该培训计划利用申请人强大的研究背景和长期- 19对女性生育的兴趣。她的目标是建立在她的技术技能,发展为一个领导者和成员 20科学界,并过渡到独立的研究。导师是一位物理科学家, 21是桩蛋白和雄激素信号传导,小鼠遗传学和卵巢生物学的世界专家,拥有悠久的历史 22成功的实习生。培训将在高度协作的环境中进行, 23.生殖研究技术方面的专门知识十分丰富。申请人已成立咨询委员会 24由卵巢生物学、桩蛋白、类固醇信号传导和microRNA测序方面的世界专家组成。她将 25利用大学主办的课程,在翻译研究方法,领导和专业 26发展,以及研究研讨会,国家会议和一对一的指导。于年底 27项目,她计划写几篇第一作者出版物,独立运行一个实验室,指导一名研究生 28、申请R-01补助金

项目成果

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Olga Igor Astapova其他文献

Olga Igor Astapova的其他文献

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{{ truncateString('Olga Igor Astapova', 18)}}的其他基金

Paxillin and Androgens in the Regulation of Ovarian Follicle Development
桩蛋白和雄激素在卵巢卵泡发育调节中的作用
  • 批准号:
    10525097
  • 财政年份:
    2022
  • 资助金额:
    $ 15.87万
  • 项目类别:
Mechanistic studies of a PPAR-g mutation that causes lipodystrophy & diabetes
导致脂肪营养不良的 PPAR-g 突变的机制研究
  • 批准号:
    8321025
  • 财政年份:
    2009
  • 资助金额:
    $ 15.87万
  • 项目类别:
Mechanistic studies of a PPAR-g mutation that causes lipodystrophy & diabetes
导致脂肪营养不良的 PPAR-g 突变的机制研究
  • 批准号:
    8133371
  • 财政年份:
    2009
  • 资助金额:
    $ 15.87万
  • 项目类别:
Mechanistic studies of a PPAR-g mutation that causes lipodystrophy & diabetes
导致脂肪营养不良的 PPAR-g 突变的机制研究
  • 批准号:
    8531227
  • 财政年份:
    2009
  • 资助金额:
    $ 15.87万
  • 项目类别:
Mechanistic studies of a PPAR-gamma mutation that causes lipodystrophy & diabetes
导致脂肪营养不良的 PPAR-gamma 突变的机制研究
  • 批准号:
    7806896
  • 财政年份:
    2009
  • 资助金额:
    $ 15.87万
  • 项目类别:

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