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
• 负责人: Sangmoo Jeong
• 金额: $ 24.9万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10359185
• 关键词: Achievement; Acute Myelocytic Leukemia; Address; Award; Benchmarking; Biochemical Reaction; Biomedical Engineering; Biopsy; Bone Marrow Cells; Cancer Biology; Cancer Model; Cell Survival; Cells; Cellular Metabolic Process; Clinical; Data; Dependence; Detection; Development; Disease; Disease model; Electrical Engineering; Engineering; Enzymes; Experimental Designs; Funding; Gatekeeping; Genetic; Goals; Hematopoietic; In Vitro; International; Label; Lead; Leukemic Cell; Magnetism; Malignant Neoplasms; Mass Spectrum Analysis; Mentors; Mentorship; Metabolic; Metabolic Marker; Metabolic Pathway; Metabolism; Microfluidics; Microscopy; Miniaturization; Molecular Analysis; Monitor; Mus; Nuclear Magnetic Resonance; Optics; Organoids; Outcome; Oxidation-Reduction; Parents; Pathway interactions; Patients; Pharmacotherapy; Phase; Preparation; Pyruvate; Reaction; Recurrence; Relaxation; Research; Resistance; Sampling; Serine; Signal Transduction; System; Techniques; Technology; Testing; Therapeutic; Time; Training; United States National Institutes of Health; Work; acute myeloid leukemia cell; advanced system; cancer cell; cancer stem cell; career; clinically relevant; conventional therapy; dehydroascorbate; diagnostic biomarker; experience; experimental analysis; high throughput analysis; in vivo; inhibitor; interest; knock-down; leukemia; leukemia initiating cell; leukemic stem cell; leukemogenesis; metabolic abnormality assessment; metabolic imaging; miniaturize; new technology; new therapeutic target; novel; novel diagnostics; predictive marker; prototype; sensor technology; skills; stem cell model; stemness; therapeutic target; therapeutically effective; tool; treatment effect; treatment response; tumor; tumor metabolism

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.

项目总结/文摘