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）：该提案是针对新的Q-TRAP 4000 LC-MS/MS系统，既可以增强我们的质谱资源的现有功能，最终替换了当前正在使用的老化的Quattrolc。当前的质谱资源位于中央仪器设施（CIF），Karmanos癌症研究所（KCI）的药理学核心以及韦恩州立大学的蛋白质组学核心。其中，只有CIF和药理学核心提供LC-MS/MS功能。参与教师的研究的主要领域之一是鉴定和/或定量小分子，例如炎症的脂质介质，饮食成分的抗癌天然产物等。其他关注的主要领域是与癌症有关的信号转导。目前，研究项目利用了分布在校园三个核心设施之间的现有质谱资源。虽然CIF和蛋白质组学核心可用的飞行时间（TOF）仪器用于蛋白质识别工作，但CIF和药理学核心的三倍四极杆仪器用于结构识别和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是参与该提案的研究人员进行小分子分析的主要资源。尽管这些研究者仍具有功能性，并且大量用于小分子定量和肽测序工作，但其在纳摩尔范围内的敏感性不足以分析和鉴定生物标志物。此外，该仪器已有七年多的历史，经常需要服务。拟议的Q-TRAP LC-MS/MS系统将提供的许多项目都需要在FMOL范围内进行检测限，以及快速的MRM扫描能力，以鉴定和定量炎症和癌症的生物标志物。此外，对于肽测序中的研究项目，新系统的蛋白质组学能力以及纳米喷雾离子源将非常有价值，以鉴定相互作用的蛋白质的化学交叉链接结构域。参与该提案的教师的研究项目由NIH不断资助，其中一些超过二十年，而Q-TRAP 4000 LC-MS/MS系统将是其继续成功的必不可少的资源。此外，该工具将催化韦恩州立大学急需的脂质核心核心设施的设置。 公共卫生相关性：所需的LC-MS/MS系统的类型用于测量生物样品中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志物。鉴定新的生物标志物以及促进早期检测，诊断和治疗的已知疾病生物标志物的验证是该仪器的主要目的。

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

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

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

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

Manganese-stimulated redox cycling of dopamine derivatives: Implications for manganism.

锰刺激的多巴胺衍生物的氧化还原循环：对锰中毒的影响。

• DOI: 10.1016/j.neuro.2022.02.007
• 发表时间: 2022
• 期刊: Neurotoxicology
• 影响因子: 3.4
• 作者: Marwah,PraneetKaur;Paik,Gijong;Issa,ChristopherJ;Jemison,ChristopherC;Qureshi,MuhammadB;Hanna,TareqM;Palomino,Eduardo;Maddipati,KrishnaRao;Njus,David
• 通讯作者: Njus,David