Thyroid Hormone Signaling in Human Hepatocytes

人肝细胞中的甲状腺激素信号传导

基本信息

  • 批准号:
    10874207
  • 负责人:
  • 金额:
    $ 33.63万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-06-30 至 2025-01-31
  • 项目状态:
    未结题

项目摘要

Project Summary Thyroid hormone is a critical mediator of development and physiologic function in adulthood. It acts on every cell type through both genomic and non-genomic mechanisms that have not been clearly defined in humans. Much of our insight into thyroid hormone action comes from mouse genetic models which appear to mimic human physiology given the conservation of the hypothalamic-pituitary thyroid axis. In addition, human diseases, such as resistance to thyroid hormone, have validated the use of mouse models but major question remain in context of cell specificity and unique paradigms that may occur in human cell types. Work in human systems has been extremely limited because of the lack of models that are thyroid hormone responsive. To get around this and begin to understand thyroid hormone action in humans we have developed human hepatocytes from induced pluripotent stem cells (iPSCs) that are highly TH responsive. Furthermore, using this unique model and gene editing techniques we can also model human disease at the cellular level. To gain further insight into human thyroid hormone action we propose three specific aims. In the first Aim we will determine the role of thyroid hormone receptor isoforms both in context of physiologic pathways engaged and genomic targets engaged. In the second Aim we will use our human hepatocyte model along with mouse genetic models to understand the role of thyroid hormone signaling in the regulation of metabolic liver disease in response to dietary challenges. Finally, in the third Aim we will use the CRISPR-Cas9 system to develop human disease models of thyroid hormone signaling, to both identify novel therapeutic pathways but also to aid in understanding the phenotype present in patients. Together completion of these Aims will provide key insight into how thyroid hormone signal in human cells both in context of normal physiology but also in disease states and open up new avenues to target these pathways in the treatment of metabolic disease.
项目总结

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)

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ANTHONY N HOLLENBERG其他文献

ANTHONY N HOLLENBERG的其他文献

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{{ truncateString('ANTHONY N HOLLENBERG', 18)}}的其他基金

Thyroid Follicular Cell Signaling and Development in Humans
人类甲状腺滤泡细胞信号传导和发育
  • 批准号:
    10801642
  • 财政年份:
    2023
  • 资助金额:
    $ 33.63万
  • 项目类别:
Hypothalamic regulation by thyroid hormone receptor phosphorylation
甲状腺激素受体磷酸化对下丘脑的调节
  • 批准号:
    10717820
  • 财政年份:
    2023
  • 资助金额:
    $ 33.63万
  • 项目类别:
Corepressor regulation of nuclear receptor action
核受体作用的辅阻遏物调节
  • 批准号:
    10562608
  • 财政年份:
    2022
  • 资助金额:
    $ 33.63万
  • 项目类别:
Thyroid Hormone Signaling in Human Hepatocytes
人肝细胞中的甲状腺激素信号传导
  • 批准号:
    9902423
  • 财政年份:
    2019
  • 资助金额:
    $ 33.63万
  • 项目类别:
Thyroid Hormone Signaling in Human Hepatocytes
人肝细胞中的甲状腺激素信号传导
  • 批准号:
    10087920
  • 财政年份:
    2019
  • 资助金额:
    $ 33.63万
  • 项目类别:
Thyroid Hormone Signaling in Human Hepatocytes
人肝细胞中的甲状腺激素信号传导
  • 批准号:
    10337213
  • 财政年份:
    2019
  • 资助金额:
    $ 33.63万
  • 项目类别:
Corepressor regulation of nuclear receptor action
核受体作用的辅阻遏物调节
  • 批准号:
    9701510
  • 财政年份:
    2018
  • 资助金额:
    $ 33.63万
  • 项目类别:
Thyroid Follicular Cell Development in Mice and Humans
小鼠和人类甲状腺滤泡细胞的发育
  • 批准号:
    9697589
  • 财政年份:
    2018
  • 资助金额:
    $ 33.63万
  • 项目类别:
Thyroid Follicular Cell Signaling and Development in Humans
人类甲状腺滤泡细胞信号传导和发育
  • 批准号:
    10435571
  • 财政年份:
    2015
  • 资助金额:
    $ 33.63万
  • 项目类别:
Thyroid Follicular Cell Development in Mice and Humans
小鼠和人类甲状腺滤泡细胞的发育
  • 批准号:
    9035478
  • 财政年份:
    2015
  • 资助金额:
    $ 33.63万
  • 项目类别:

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Thyroid Hormone Signaling and Cone Photoreceptor Degeneration
甲状腺激素信号传导和视锥细胞变性
  • 批准号:
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  • 财政年份:
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  • 财政年份:
    2021
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Spatiotemporal regulation of thyroid hormone signaling in cone subtype specification in human retinal organoids
人视网膜类器官视锥亚型规范中甲状腺激素信号传导的时空调节
  • 批准号:
    10687129
  • 财政年份:
    2021
  • 资助金额:
    $ 33.63万
  • 项目类别:
Spatiotemporal regulation of thyroid hormone signaling in cone subtype specification in human retinal organoids
人视网膜类器官视锥亚型规范中甲状腺激素信号传导的时空调节
  • 批准号:
    10312633
  • 财政年份:
    2021
  • 资助金额:
    $ 33.63万
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Understanding the role of thyroid hormone signaling during axolotl limb regeneration
了解甲状腺激素信号在蝾螈肢体再生过程中的作用
  • 批准号:
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  • 财政年份:
    2020
  • 资助金额:
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  • 项目类别:
Thyroid Hormone Signaling in Human Hepatocytes
人肝细胞中的甲状腺激素信号传导
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    9902423
  • 财政年份:
    2019
  • 资助金额:
    $ 33.63万
  • 项目类别:
Thyroid Hormone Signaling in Human Hepatocytes
人肝细胞中的甲状腺激素信号传导
  • 批准号:
    10087920
  • 财政年份:
    2019
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Thyroid Hormone Signaling in Human Hepatocytes
人肝细胞中的甲状腺激素信号传导
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    10337213
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Epithelial Protective Effects of Thyroid Hormone Signaling in Fibrosis
甲状腺激素信号传导对纤维化的上皮保护作用
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    10307633
  • 财政年份:
    2018
  • 资助金额:
    $ 33.63万
  • 项目类别:
Epithelial Protective Effects of Thyroid Hormone Signaling in Fibrosis
甲状腺激素信号传导对纤维化的上皮保护作用
  • 批准号:
    10063549
  • 财政年份:
    2018
  • 资助金额:
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