Hyperpolarized Micro-NMR for Quantitative Analysis of Metabolism in Leukemia Stem Cells

用于白血病干细胞代谢定量分析的超极化微核磁共振

基本信息

  • 批准号:
    10544545
  • 负责人:
  • 金额:
    $ 24.9万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-03-01 至 2024-12-31
  • 项目状态:
    已结题

项目摘要

Project Summary/Abstract The overarching goal of this project is to acquire the skills necessary to launch a competitive, independent research career in the field of biomedical engineering, with an explicit specialization in cancer metabolism research. Aberrant metabolic features in cancer cells, now recognized as one of the hallmarks of cancer, can be novel diagnostic biomarkers or therapeutic targets. Unfortunately, understanding of cancer metabolism remains limited, which is primarily due to the lack of tools. My long- term career goal is to lead a competitive research group, with primary research interests in developing novel technologies that allow sensitive and high-throughput analysis of cancer metabolism. I have extensive experience in developing sensitive analytical platforms with a background in electrical engineering. In addition to my engineering expertise, the mentorship from internationally recognized experts in cancer biology during the K99 training period will be instrumental towards my career objectives. In the current research, I plan to develop a novel magnetic sensing technology for comprehensive analysis of metabolism in leukemia stem cells (LSCs), as well as to acquire a deeper understanding of cancer biology. The Research Plan is built upon the development of the hyperpolarized micro nuclear magnetic resonance (HP micro-NMR) technology that enables quantitative analysis of metabolic flux in a small number of cells (down to 104 cells) within two minutes, while maintaining more than 90% of cell viability. The novel platform I developed, importantly, allowed downstream molecular analyses in the same sample in tandem, which may be truly beneficial for investigating mass-limited samples. Here, I will advance this system further to achieve a higher sensitivity and enhanced analytical throughput for comprehensive analysis of LSC metabolism (Aim 1), and I will develop HP metabolic markers to identify the dependence of LSCs on a metabolic enzyme, PHGDH, which has emerged as a promising therapeutic target for other cancers (Aim 2). The focus of the current research is centered on the critical clinical need for relevant leukemia stem cells models, but with imperative funding from the NIH Pathway to Independence Award - Parent K99/R00, the proposed platform would extend much further and have wide applicability on other clinically relevant cancer models, such as patient biopsies or tumor organoids.
项目概要/摘要 该项目的总体目标是获得启动有竞争力的、 在生物医学工程领域的独立研究生涯,明确的专业是 癌症代谢研究。癌细胞中异常的代谢特征,现在被认为是 癌症的标志,可以是新的诊断生物标志物或治疗靶点。很遗憾, 对癌症代谢的了解仍然有限,这主要是由于缺乏工具。我的长- 学期职业目标是领导一个有竞争力的研究小组,主要研究兴趣是开发 允许对癌症代谢进行灵敏和高通量分析的新技术。我有 在开发具有电气背景的敏感分析平台方面拥有丰富的经验 工程。除了我的工程专业知识之外,还得到国际公认的指导 K99 培训期间的癌症生物学专家将对我的职业生涯发挥重要作用 目标。在目前的研究中,我计划开发一种新颖的磁传感技术 全面分析白血病干细胞(LSC)的代谢,并获得更深入的了解 了解癌症生物学。该研究计划建立在超极化的发展基础上 微核磁共振 (HP micro-NMR) 技术可实现对 两分钟内少量细胞(低至 104 个细胞)的代谢通量,同时保持更多 超过90%的细胞活力。重要的是,我开发的新颖平台允许下游分子 对同一样品进行串联分析,这可能真正有利于研究质量限制 样品。在这里,我将进一步改进该系统,以实现更高的灵敏度和增强的分析能力 综合分析LSC代谢(目标1)的吞吐量,我将开发HP代谢 标记来识别 LSC 对代谢酶 PHGDH 的依赖性,PHGDH 已成为一种 其他癌症有希望的治疗靶点(目标 2)。目前的研究重点集中在 相关白血病干细胞模型的关键临床需求,但需要 NIH 的资助 独立之路奖 - 母版 K99/R00,拟议的平台将进一步扩展 并在其他临床相关癌症模型上具有广泛的适用性,例如患者活检或肿瘤 类器官。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Hyperpolarized Micro-NMR Platform for Sensitive Analysis of In Vitro Metabolic Flux in Living Cells.
Multi-sample measurement of hyperpolarized pyruvate-to-lactate flux in melanoma cells.
  • DOI:
    10.1002/nbm.4447
  • 发表时间:
    2021-03
  • 期刊:
  • 影响因子:
    2.9
  • 作者:
    Lees H;Millan M;Ahamed F;Eskandari R;Granlund KL;Jeong S;Keshari KR
  • 通讯作者:
    Keshari KR
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Sangmoo Jeong其他文献

Sangmoo Jeong的其他文献

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{{ truncateString('Sangmoo Jeong', 18)}}的其他基金

Metabolic regulation of exosome biogenesis
外泌体生物发生的代谢调节
  • 批准号:
    10798893
  • 财政年份:
    2022
  • 资助金额:
    $ 24.9万
  • 项目类别:
Metabolic regulation of exosome biogenesis
外泌体生物发生的代谢调节
  • 批准号:
    10668526
  • 财政年份:
    2022
  • 资助金额:
    $ 24.9万
  • 项目类别:
Hyperpolarized Micro-NMR for Quantitative Analysis of Metabolism in Leukemia Stem Cells
用于白血病干细胞代谢定量分析的超极化微核磁共振
  • 批准号:
    10359185
  • 财政年份:
    2018
  • 资助金额:
    $ 24.9万
  • 项目类别:
Hyperpolarized Micro-NMR for Quantitative Analysis of Metabolism in Leukemia Stem Cells
用于白血病干细胞代谢定量分析的超极化微核磁共振
  • 批准号:
    10305913
  • 财政年份:
    2018
  • 资助金额:
    $ 24.9万
  • 项目类别:

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  • 批准号:
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  • 批准号:
    3556971
  • 财政年份:
    1980
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  • 项目类别:
DETERMINANTS OF RESPONSE OF ACUTE MYELOCYTIC LEUKEMIA
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    3556968
  • 财政年份:
    1980
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ERADICATION OF ACUTE MYELOCYTIC LEUKEMIA CELLS BY MAB THERAPY
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