Triple Quadrupole - Ion Trap Hybrid LC/MS/MS System

三重四极杆 - 离子阱混合 LC/MS/MS 系统

• 批准号: 7795525
• 负责人: Krishnarao Maddipati
• 金额: $ 42.53万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-22 至 2011-04-21
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7795525
• 关键词: 7 year old; Aging; Area; Biological; Biological Factors; Biological Markers; Clinical Trials; Core Facility; Detection; Diagnosis; Disease; Drug Kinetics; Early Diagnosis; Faculty; Funding; Hybrids; Inflammation; Institutes; Ions; Malignant Neoplasms; Mass Spectrum Analysis; Measurement; Pharmacology; Proteins; Proteomics; Research; Research Personnel; Research Project Grants; Resources; Sampling; Scanning; Services; Signal Transduction; Structure; System; Time; United States National Institutes of Health; Universities; Validation; Work; crosslink; drug metabolism; instrument; interest; ion source; lipid mediator; novel; protein aminoacid sequence; public health relevance; small molecule; success

DESCRIPTION (provided by applicant): This proposal is for a new Q-TRAP 4000 LC-MS/MS system, both to enhance the existing capabilities of our mass spectrometry resources and eventually to replace the aging QuattroLC that is currently in use. The current mass spectrometry resources are located at the Central Instrument Facility (CIF), the Pharmacology Core of the Karmanos Cancer Institute (KCI), and the Proteomics Core of Wayne State University. Of these, only the CIF and Pharmacology Core offer LC-MS/MS capability. One of the major areas of the participating faculty's research involves identification and/or quantitation of small molecules such as, lipid mediators of inflammation, anticancer natural products from dietary ingredients, etc. The other major area of interest is the signal transduction pertaining to cancer. The research projects currently utilize the existing mass spectrometry resources distributed among three core facilities on campus. While the Time of Flight (TOF) instruments available at CIF and Proteomics Core are used for the protein identification work, the triple quadrupole instruments at CIF and Pharmacology Core are used for structure identification and LC-MS quantitation. Of these, the LC-MS of Pharmacology Core is primarily used by KCI researchers for drug metabolism, pharmacokinetics, and clinical trials. The QuattroLC at the CIF is the primary resource for small molecule analysis by the investigators participating in this proposal. While this instrument is still functional and heavily used by these investigators for small molecule quantitation and peptide sequencing work, its sensitivity in the nanomolar range is inadequate for the analysis and identification of biomarkers. Moreover, this instrument is more than seven years old and is frequently in need of service. Many of the projects that will be served by the proposed Q-TRAP LC- MS/MS system require detection limits in the fmol range as well as fast MRM scan capability for the identification and quantification of biomarkers of inflammation and cancer. Additionally, the proteomics capability of the new system along with the Nanospray ion source, would be immensely valuable for the research projects in peptide sequencing to identify chemically cross linked domains of interacting proteins. Research projects of the faculty participating in this proposal are continuously funded by NIH, some for more than two decades, and the Q-TRAP 4000 LC-MS/MS system would be an indispensable resource for their continued success. Additionally, this instrument will catalyze the setup of a much needed Lipidomics core facility at Wayne State University. PUBLIC HEALTH RELEVANCE: The type of LC-MS/MS system requested is used for the measurement of small molecule analytes present at extremely low concentrations in biological samples. These include biomarkers of inflammation, cancer, and related diseases. Identification of novel biomarkers and validation of known biomarkers of diseases that facilitate early detection, diagnosis, and treatment is the primary purpose of this instrument.

描述(由申请人提供)：这项建议是为了建立一个新的Q-Trap 4000 LC-MS/MS系统，以增强我们的质谱学资源的现有能力，并最终取代目前正在使用的老化的QuattroLC。目前的质谱学资源位于中央仪器设施(CIF)、卡马诺斯癌症研究所(KCI)的药理学核心和韦恩州立大学的蛋白质组学核心。其中，只有CIF和Pharmacology Core提供LC-MS/MS功能。参与研究的主要领域之一涉及识别和/或定量小分子，如炎症的脂质介质、来自饮食成分的抗癌天然产品等。另一个感兴趣的主要领域是与癌症有关的信号转导。这些研究项目目前利用了分布在校园三个核心设施中的现有质谱学资源。CIF和蛋白质组学中心的飞行时间(TOF)仪器用于蛋白质鉴定工作，CIF和Pharmacology Core的三重四极杆仪器用于结构鉴定和LC-MS定量。其中，药理学核心的LC-MS主要由KCI研究人员用于药物代谢、药代动力学和临床试验。CIF的QuattroLC是参与这项提议的研究人员进行小分子分析的主要资源。虽然该仪器仍在发挥作用，并被这些研究人员大量用于小分子定量和多肽测序工作，但其在纳摩尔范围内的灵敏度不足以分析和鉴定生物标记物。此外，这台仪器已有七年多的历史，经常需要维修。拟议中的Q-TRAP LC-MS/MS系统将服务于许多项目，这些项目需要fmol范围内的检测极限以及快速MRM扫描能力，以识别和量化炎症和癌症的生物标记物。此外，新系统的蛋白质组学能力以及纳米螺旋离子源，将对肽序列中识别相互作用蛋白质的化学交联域的研究项目具有极大的价值。参与这项计划的教职员工的研究项目由美国国立卫生研究院持续资助，有些项目持续资助了二十多年，而Q-TRAP 4000 LC-MS/MS系统将是他们继续成功不可或缺的资源。此外，该仪器还将催化在韦恩州立大学建立一个亟需的脂肪组学核心设施。 公共卫生相关性：所要求的LC-MS/MS系统类型用于测量生物样品中存在的极低浓度的小分子分析物。这些包括炎症、癌症和相关疾病的生物标记物。该仪器的主要目的是识别新的生物标记物，并验证有助于早期发现、诊断和治疗的已知疾病生物标记物。

项目成果

NDRG1 regulates neutral lipid metabolism in breast cancer cells.

• DOI: 10.1186/s13058-018-0980-4
• 发表时间: 2018-06-14
• 期刊: Breast cancer research : BCR
• 作者: Sevinsky CJ;Khan F;Kokabee L;Darehshouri A;Maddipati KR;Conklin DS
• 通讯作者: Conklin DS

Fat Composition Measured by Proton Spectroscopy: A Breast Cancer Tumor Marker?

• DOI: 10.3390/diagnostics11030564
• 发表时间: 2021-03-21
• 期刊: Diagnostics (Basel, Switzerland)
• 作者: Bitencourt A;Sevilimedu V;Morris EA;Pinker K;Thakur SB
• 通讯作者: Thakur SB

Parenteral Fish-Oil Containing Lipid Emulsions Limit Initial Lipopolysaccharide-Induced Host Immune Responses in Preterm Pigs.

• DOI: 10.3390/nu13010205
• 发表时间: 2021-01-12
• 期刊: Nutrients
• 影响因子: 5.9
• 作者: Yakah W;Ramiro-Cortijo D;Singh P;Brown J;Stoll B;Kulkarni M;Oosterloo BC;Burrin D;Maddipati KR;Fichorova RN;Freedman SD;Martin CR
• 通讯作者: Martin CR

Author Correction: Identification of specialized pro-resolving mediator clusters from healthy adults after intravenous low-dose endotoxin and omega-3 supplementation: a methodological validation.

作者更正：静脉注射低剂量内毒素和 omega-3 补充剂后从健康成人中鉴定专门的促分解介质簇：方法学验证。

• DOI: 10.1038/s41598-019-56282-5
• 发表时间: 2019
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Norris,PaulC;Skulas-Ray,AnnC;Riley,Ian;Richter,ChesneyK;Kris-Etherton,PennyM;Jensen,GordonL;Serhan,CharlesN;Maddipati,KrishnaRao
• 通讯作者: Maddipati,KrishnaRao

Neuronal porosome lipidome.

• DOI: 10.1111/jcmm.12383
• 发表时间: 2014-10
• 期刊: Journal of cellular and molecular medicine
• 影响因子: 5.3
• 作者: Lewis KT;Maddipati KR;Taatjes DJ;Jena BP
• 通讯作者: Jena BP