权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Implementing Photodissociation Mass Spectrometry to study Disease and Lipid Structure

利用光解离质谱研究疾病和脂质结构

基本信息

批准号：
10377907
负责人：
Luis A Macias
金额：
$ 1.22万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-10 至 2022-06-01
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10377907
关键词：
Address Advanced Development Affect Biological Biological Markers Cancerous Cardiolipins Cardiovascular Diseases Cell physiology Cells Cellular Membrane Collaborations Complex Coupled Development Diabetes Mellitus Disease Dissociation Fatty Acids Glycerophospholipids Hormone Receptor Imaging Techniques Inner mitochondrial membrane Ions Isomerism Lasers Lipids Location Malignant Neoplasms Mammary Neoplasms Mass Spectrum Analysis Membrane Metabolic Methods Mitochondria Nerve Degeneration Nucleotides Pathway interactions Phospholipids Physiologic pulse Positioning Attribute Progesterone Receptor Status Prognostic Marker Proteins Reporting Respiratory Process Role Sampling Signal Pathway Signal Transduction Specificity Structure Techniques Tissues Tumor Subtype Tumor Tissue Work anticancer research cancer cell cancer subtypes cohort diagnostic biomarker diagnostic tool experimental study high throughput analysis insight lipid metabolism lipid structure lipidomics malignant breast neoplasm new therapeutic target pi bond potential biomarker protein function protein structure specific biomarkers stereochemistry success tandem mass spectrometry theories therapeutic target tool tumor tumorigenesis ultraviolet

项目摘要

Abstract Lipids fulfill an array of cellular functions by composing cellular membranes, engaging in signaling pathways, and modulating protein structure. Disruptions in carefully regulated lipid compositions perturb cellular function and correlate with cancer, neurodegeneration, diabetes, and cardiovascular disease. The correlation between aberrant lipid composition and disease has inspired lipid profiling as a powerful diagnostic tool. Analysis of structural changes that concur with disease promises to reveal highly specific biomarkers and insight into the disease development. This proposal focuses on the development of ultraviolet photodissociation (UVPD) tandem mass spectrometry approaches for the characterization of glycerophospholipids (GPL) and the cardiolipin (CL) subtype in cancerous tissue. Cancer induces a stark metabolic shift that significantly affects lipid metabolism. UVPD is a high-energy ion activation technique used for MS/MS analysis, informing subtle features that are not captured by other mass spectrometry methods. Implementing UVPD to track changes in tumorous GPL structures with fine detail offers an avenue to explore the full effects of cancer on lipid dysregulation. The objectives of this proposal include: Aim 1: Development of an LC-MS-UVPD workflow to identify changes in phospholipid structure between breast cancer tissue subtypes. A quantitative lipidomic workflow incorporating UVPD will be developed for the high-throughput analysis of GPL isomers. The proposed strategy will be applied to analyze a cohort of breast tumor lipid extracts and identify significant structural changes and prognostic biomarkers. Aim 2: Complete characterization of cardiolipins from cancer cells using UVPD. CLs are of particular relevance for cancer research but present challenging structures. UVPD is the only activation method reported to provide detailed CL characterization and will be expanded upon to characterize CLs from tumorous tissue. All together, the proposed strategies promise avenues to identify diagnostic biomarkers, potential therapeutic targets, and disease mechanisms. Importantly, these strategies would be applicable for lipidomic analyses of GPLs and CLs from other diseases.

摘要脂质通过组成细胞膜，参与信号通路，和调节蛋白质结构。仔细调节的脂质组成的破坏扰乱细胞功能并与癌症、神经退化、糖尿病和心血管疾病相关。的相关性异常的脂质组成和疾病激发了脂质谱分析作为一种强大的诊断工具。分析与疾病同时发生的结构变化有望揭示高度特异性的生物标志物，并深入了解疾病发展。本论文主要研究紫外光解离（UVPD）串联技术用于表征甘油磷脂（GPL）和心磷脂（CL）的质谱法癌组织中的亚型。癌症引起显著影响脂质代谢的明显代谢转变。 UVPD是一种用于MS/MS分析的高能离子活化技术，可提供不需要的细微特征。通过其他质谱方法捕获。实施UVPD以跟踪肿瘤GPL的变化具有精细细节的结构提供了一种探索癌症对脂质失调的全面影响的途径。的该提案的目标包括：目标1：开发LC-MS-UVPD工作流程，以确定乳腺癌组织亚型之间的磷脂结构。一种定量脂质组学工作流程， UVPD将被开发用于GPL异构体的高通量分析。拟议战略将适用于分析一组乳腺肿瘤脂质提取物，并确定显著的结构变化和预后生物标志物。目的2：使用UVPD完全表征来自癌细胞的心磷脂。CL特别是与癌症研究相关，但目前具有挑战性的结构。UVPD是唯一报道的活化方法以提供详细的CL表征，并将扩展到表征来自肿瘤组织的CL。所有总而言之，所提出的策略为识别诊断生物标志物、潜在的治疗方法提供了途径目标和疾病机制。重要的是，这些策略将适用于脂质组学分析，其他疾病的GPL和CL。