Double Duty: Elucidating the Effects of Estrogen on Tumor Cells and their Microenvironment in Lymphangioleiomyomatosis

双重职责:阐明雌激素对淋巴管平滑肌瘤病中肿瘤细胞及其微环境的影响

基本信息

  • 批准号:
    10693206
  • 负责人:
  • 金额:
    $ 4.77万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-09-01 至 2024-08-31
  • 项目状态:
    已结题

项目摘要

Project Summary Affecting almost exclusively women, lymphangioleiomyomatosis (LAM) is a rare lung disease characterized by estrogen-sensitive metastatic smooth muscle cell-like adenomas that grow slowly, resulting in cystic lung change and loss of pulmonary function. While mTORC1 disinhibition due to loss of TSC1 or TSC2 mediates the development of this malignancy, estrogen play a key role in promoting LAM tumor growth. The Hammes laboratory created a mouse model for LAM whereby TSC2 was specifically knocked out in the uterus of female mice. These animals developed estrogen-sensitive myometrial tumors that shared most characteristics of LAM tumor cells. Interesting, 50% of animals developed lung metastasis, suggesting that LAM cells may come from the myometrium, thus explaining the sexual dimorphism and estrogen sensitivity of LAM. Importantly, while TSC2-null in-vivo tumors were markedly sensitive to estradiol, TSC2-null cell lines are only mildly estrogen- sensitive, suggesting that estrogen may have actions outside of the TSC2-null cells that promote tumor growth. This research proposal focuses on the potential dual effector function of estradiol in promoting LAM progression. The research strategy is designed to examine estrogen modulation of LAM cells as well as their microenvironment. The proposal concentrates specifically on estrogen actions in granulocytic myeloid-derived suppressor cells, which are markedly elevated in the blood and uteri of uterine-specific TSC2-null mice and play a significant role in promoting tumor progression, likely in an estrogen-dependent fashion. These studies will utilize the novel mouse model, TSC2-null xenografts, in-vitro bone marrow stimulation assays, and other methods to determine mechanisms by which estrogen directly promotes TSC2-null cell growth and indirectly promotes myeloid derived suppressor cell production and actions. This fellowship will provide a path for a highly qualified candidate into a career as a physician scientist. The Hammes laboratory has an extensive background in cancer research, mouse genetics, and steroid signaling. The scope of the lab is continuously expanding as it explores the role of innate immunity in cancer models. In addition, the applicant has assembled an advisory committee comprised of experts in hormone signaling, inflammation, and tumor immunology. Her training plan includes courses in ethics, leadership and professional development, as well as research seminars, national meetings and one-on-one instruction. She has positioned herself optimally to achieve these goals under the mentorship of Dr. Hammes, a role model physician scientist with a long track record of training successful investigators in basic and translational research. The institutional environment at Rochester emphasizes and supports collaborative research and is invested in training future physicians and scientists. The knowledge gained from this fellowship will advance the field of LAM research, propose an estrogen-centered strategy for treatment, and fortify the career development of a young trainee devoted to being a physician scientist.
项目摘要 淋巴管平滑肌瘤病(LAM)几乎只影响女性,是一种罕见的肺部疾病,其特征是 雌激素敏感的转移性平滑肌细胞样腺瘤,生长缓慢,导致囊性肺改变 以及肺功能丧失虽然由于TSC 1或TSC 2的缺失而导致的mTORC 1去抑制介导了细胞凋亡。 在这种恶性肿瘤的发展中,雌激素在促进LAM肿瘤生长中起关键作用。哈姆斯 一个实验室创建了一个LAM的小鼠模型,其中TSC 2在雌性小鼠的子宫中被特异性敲除。 小鼠这些动物发生了雌激素敏感的子宫肌层肿瘤,具有LAM的大部分特征 肿瘤细胞有趣的是,50%的动物发生了肺转移,这表明LAM细胞可能来自 子宫肌层,从而解释了LAM的性二型性和雌激素敏感性。重要的是,虽然 TSC 2-null体内肿瘤对雌二醇显著敏感,TSC 2-null细胞系仅轻度雌激素敏感。 这表明雌激素可能在TSC 2无效细胞之外具有促进肿瘤生长的作用。 这项研究计划的重点是雌二醇在促进LAM进展中的潜在双重效应功能。 该研究策略旨在检查LAM细胞的雌激素调节以及它们的细胞周期。 微环境。该提案专门集中在雌激素作用于粒细胞髓源性 在子宫特异性TSC 2缺失小鼠的血液和子宫中显著升高的抑制细胞, 可能以雌激素依赖的方式在促进肿瘤进展中起重要作用。这些研究将 利用新的小鼠模型、TSC 2缺失异种移植物、体外骨髓刺激测定和其他 确定雌激素直接促进TSC 2缺失细胞生长和间接促进TSC 2缺失细胞生长的机制的方法。 促进髓源性抑制细胞的产生和作用。这个奖学金将提供一个高度的路径, 合格的候选人成为一名医生科学家。哈姆斯实验室有着广泛的背景 在癌症研究、小鼠遗传学和类固醇信号传导方面。实验室的范围不断扩大, 探索先天免疫在癌症模型中的作用。此外,申请人还召集了一个咨询小组, 该委员会由激素信号、炎症和肿瘤免疫学专家组成。她的训练计划 包括道德,领导力和专业发展课程,以及研究研讨会,国家 会议和一对一的指导。她已经为实现这些目标做好了最佳准备, Hammes博士的指导,Hammes博士是一位模范医生科学家,长期以来一直在成功培训 基础研究和转化研究的研究者。罗切斯特的制度环境强调, 支持合作研究,并投资于培训未来的医生和科学家。知识 从这项奖学金中获得的将推进LAM研究领域,提出以雌激素为中心的策略, 治疗,并加强一个年轻的实习生的职业发展,致力于成为一名医生科学家。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Briaunna Monet Nyika Minor其他文献

Briaunna Monet Nyika Minor的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Briaunna Monet Nyika Minor', 18)}}的其他基金

Double Duty: Elucidating the Effects of Estrogen on Tumor Cells and their Microenvironment in Lymphangioleiomyomatosis
双重职责:阐明雌激素对淋巴管平滑肌瘤病中肿瘤细胞及其微环境的影响
  • 批准号:
    10469668
  • 财政年份:
    2020
  • 资助金额:
    $ 4.77万
  • 项目类别:
Double Duty: Elucidating the Effects of Estrogen on Tumor Cells and their Microenvironment in Lymphangioleiomyomatosis
双重职责:阐明雌激素对淋巴管平滑肌瘤病中肿瘤细胞及其微环境的影响
  • 批准号:
    10321203
  • 财政年份:
    2020
  • 资助金额:
    $ 4.77万
  • 项目类别:

相似海外基金

Hormone therapy, age of menopause, previous parity, and APOE genotype affect cognition in aging humans.
激素治疗、绝经年龄、既往产次和 APOE 基因型会影响老年人的认知。
  • 批准号:
    495182
  • 财政年份:
    2023
  • 资助金额:
    $ 4.77万
  • 项目类别:
Investigating how alternative splicing processes affect cartilage biology from development to old age
研究选择性剪接过程如何影响从发育到老年的软骨生物学
  • 批准号:
    2601817
  • 财政年份:
    2021
  • 资助金额:
    $ 4.77万
  • 项目类别:
    Studentship
RAPID: Coronavirus Risk Communication: How Age and Communication Format Affect Risk Perception and Behaviors
RAPID:冠状病毒风险沟通:年龄和沟通方式如何影响风险认知和行为
  • 批准号:
    2029039
  • 财政年份:
    2020
  • 资助金额:
    $ 4.77万
  • 项目类别:
    Standard Grant
Neighborhood and Parent Variables Affect Low-Income Preschool Age Child Physical Activity
社区和家长变量影响低收入学龄前儿童的身体活动
  • 批准号:
    9888417
  • 财政年份:
    2019
  • 资助金额:
    $ 4.77万
  • 项目类别:
The affect of Age related hearing loss for cognitive function
年龄相关性听力损失对认知功能的影响
  • 批准号:
    17K11318
  • 财政年份:
    2017
  • 资助金额:
    $ 4.77万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
  • 批准号:
    9320090
  • 财政年份:
    2017
  • 资助金额:
    $ 4.77万
  • 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
  • 批准号:
    10166936
  • 财政年份:
    2017
  • 资助金额:
    $ 4.77万
  • 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
  • 批准号:
    9761593
  • 财政年份:
    2017
  • 资助金额:
    $ 4.77万
  • 项目类别:
How age dependent molecular changes in T follicular helper cells affect their function
滤泡辅助 T 细胞的年龄依赖性分子变化如何影响其功能
  • 批准号:
    BB/M50306X/1
  • 财政年份:
    2014
  • 资助金额:
    $ 4.77万
  • 项目类别:
    Training Grant
Inflamm-aging: What do we know about the effect of inflammation on HIV treatment and disease as we age, and how does this affect our search for a Cure?
炎症衰老:随着年龄的增长,我们对炎症对艾滋病毒治疗和疾病的影响了解多少?这对我们寻找治愈方法有何影响?
  • 批准号:
    288272
  • 财政年份:
    2013
  • 资助金额:
    $ 4.77万
  • 项目类别:
    Miscellaneous Programs
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了