An Ultra-Performance Liquid Chromatography System to Support Metabolomics at Yale University

支持耶鲁大学代谢组学的超高效液相色谱系统

• 批准号: 8825610
• 负责人: TuKiet T Lam
• 金额: $ 13.52万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8825610
• 关键词: Academic Medical Centers; Aging; Autistic Disorder; Biomedical Research; Classification; Clinical; Cohort Studies; Colorado; Cornea; Coupled; Diabetes Mellitus; Ethanol Metabolism; Funding; Injury; Institution; Insulin Resistance; Knowledge; Liquid Chromatography; Lyme Disease; Mass Spectrum Analysis; Medical center; Minor; Mississippi; Modeling; Neuronal Ceroid-Lipofuscinosis; New York; Obesity; Performance; Pregnancy; Process; Proteomics; Pulmonary Sarcoidosis; Research Personnel; Resources; Sampling; Services; System; Tissues; United States National Institutes of Health; Universities; base; cohort; cost; human disease; instrument; instrumentation; interest; mass spectrometer; medical schools; melanoma; metabolomics; molecular marker; outcome forecast; pressure; prevent; prospective; protocol development; small molecule; tool

 DESCRIPTION (provided by applicant): The Yale Keck MS and Proteomics Resource has developed and integrated a high throughput metabolomics workflow that utilizes the robustness of a high flow Ultra-Pressure Liquid Chromatography (UPLC) system in an emerging mass spectrometry based model. This model is for validating and quantifying metabolites and small molecules which provide a prospective classification and confirmation of bio-molecular markers from large clinical cohorts. As evident by the current instrument usage (based on the number of samples injected), our metabolomics workflow was immediately recognized by researchers at Yale and other institutions as an important biotechnological tool to efficiently and cost effectivey process their large study cohorts. Due to our development of these protocols utilizing a demo UPLC system, we are requesting funding to purchase a permanent ACQUITY UPLC H-Class system to be coupled to our existing 4000 QTRAP mass spectrometer which is the platform the metabolomics workflow was developed on. If funded, the permanent UPLC system would provide continued access with 83% instrument usage by the 7 Major NIH-funded users who supported this application, along with 11 Minor users utilizing the remaining >17% of the requested UPLC system. These investigators from Yale, 4 nearby (Harvard, Columbia University Medical Center, U.Conn Medical Center, and New York Medical College) and 2 other US (U. of Colorado at Denver and U. of Mississippi Medical Center) Institutions propose to use our Targeted metabolomics service to advance diverse biomedical research on: Diabetes, Obesity, Pulmonary Sarcoidosis, Corneal Antiangiogensis, Alcohol metabolism, Tissue injury, Melanoma, Neuronal Ceroid Lipofuscinosis, Autism, Lyme disease, Insulin resistance in Pregnancy, and Aging. The requested UPLC system will also enable our developed metabolomics workflow to be made available to the 218 investigators from 81 institutions and companies who used the services provided by the Yale Keck MS and Proteomics Resource in 2013. Progress in this metabolomics workflow will advance knowledge of how best to understand, prevent, prognose, and treat human diseases. The requested UPLC system and the associated metabolomics workflow would be unique at Yale University, and would be available to other interested investigators due to its placement in a core resource facility that accepts samples from across the U.S. and (when needed to keep its instrumentation operating at capacity) from around the world. Thus, the UPLC system would significantly contribute to biomedical research at Yale University and beyond.

 描述（由申请人提供）：Yale Keck MS和蛋白质组学资源开发并整合了高通量代谢组学工作流程，该工作流程在新兴的基于质谱的模型中利用了高流量超高压液相色谱（UPLC）系统的稳健性。该模型用于验证和定量代谢物和小分子，其提供来自大型临床队列的生物分子标志物的前瞻性分类和确认。从目前的仪器使用情况（基于注射的样本数量）可以看出，我们的代谢组学工作流程立即被耶鲁大学和其他机构的研究人员认为是一种重要的生物技术工具，可以有效地和成本效益地处理他们的大型研究队列。由于我们使用演示UPLC系统开发这些方案，我们正在申请资金购买永久性ACQUITY UPLC H-Class系统，以连接到我们现有的4000 QTRAP质谱仪，该质谱仪是代谢组学工作流程开发的平台。如果获得资金，永久性UPLC系统将为支持该应用的7个主要NIH资助用户提供83%的仪器使用率的持续访问，沿着的还有11个次要用户，他们使用了剩余的>17%的UPLC系统。这些研究人员来自耶鲁大学、附近的4所大学（哈佛大学、哥伦比亚大学医学中心、康涅狄格大学医学中心和纽约医学院）和其他2所美国大学。在丹佛和美国科罗拉多州的科罗拉多。（密西西比医学中心）机构建议使用我们的靶向代谢组学服务来推进各种生物医学研究：糖尿病、肥胖、肺结节病、角膜抗血管生成、酒精代谢、组织损伤、黑色素瘤、神经元蜡样脂肪褐质沉积症、自闭症、莱姆病、妊娠期胰岛素抵抗和衰老。所要求的UPLC系统还将使我们开发的代谢组学工作流程能够提供给来自81个机构和公司的218名研究人员，他们在2013年使用了耶鲁大学凯克MS和蛋白质组学资源提供的服务。代谢组学工作流程的进展将促进如何最好地理解，预防，预防和治疗人类疾病的知识。所要求的UPLC系统和相关的代谢组学工作流程在耶鲁大学是独一无二的，并将提供给其他感兴趣的研究人员，因为它被放置在一个核心资源设施中，该设施接受来自美国各地的样品，并且（当需要保持其仪器的容量运行时）来自世界各地。因此，UPLC系统将大大有助于耶鲁大学及其他地区的生物医学研究。

项目成果

Identification of growth hormone receptor as a relevant target for precision medicine in low-EGFR expressing glioblastoma.

• DOI: 10.1002/ctm2.939
• 发表时间: 2022-07
• 期刊: CLINICAL AND TRANSLATIONAL MEDICINE
• 影响因子: 10.6
• 作者: Verreault, Maite;Segoviano Vilchis, Irma;Rosenberg, Shai;Lemaire, Nolwenn;Schmitt, Charlotte;Guehennec, Jeremy;Royer-Perron, Louis;Thomas, Jean-Leon;Lam, TuKiet T.;Dingli, Florent;Loew, Damarys;Ducray, Francois;Paris, Sophie;Carpentier, Catherine;Marie, Yannick;Laigle-Donadey, Florence;Rousseau, Audrey;Pigat, Natascha;Boutillon, Florence;Bielle, Franck;Mokhtari, Karima;Frank, Stuart J.;de Reynies, Aurelien;Hoang-Xuan, Khe;Sanson, Marc;Goffin, Vincent;Idbaih, Ahmed
• 通讯作者: Idbaih, Ahmed