Pharmacometabolomics Research Network

药物代谢组学研究网络

• 批准号: 7935819
• 负责人: Rima F Kaddurah-Daouk
• 金额: $ 7.8万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-15 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7935819
• 关键词: Achievement; Address; Adverse reactions; Affect; Alberta province; Animal Model; Animals; Antihypertensive Agents; Area; Atherosclerosis; Award; Biochemical; Biochemical Pathway; Biochemistry; Bioinformatics; Biological; Biological Assay; Biological Markers; Biological Models; Biomedical Research; Body Fluids; Cardiovascular system; Cell Culture System; Cell Line; Cells; Clinical; Communities; Complement; Complex; DNA Resequencing; Data; Data Analyses; Databases; Detection; Development; Diagnosis; Discipline; Disease; Drug Exposure; Drug Monitoring; Drug effect disorder; Drug usage; Electrochemistry; Environment; Enzymes; Florida; Foundations; Future; Gene Expression; Generations; Genes; Genetic Polymorphism; Genome; Genomics; Genotype; Glucose; Goals; Health Status; Heart; Hypertension; Inborn Errors of Metabolism; Individual; Informatics; Injury; Institution; Interdisciplinary Study; Investments; Knowledge; LDL Cholesterol Lipoproteins; Maps; Mass Spectrum Analysis; Measures; Medical; Mental Depression; Metabolic; Mind; Modeling; Molecular; NIH Program Announcements; Non-Insulin-Dependent Diabetes Mellitus; Pathway Analysis; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacogenetics; Pharmacogenomics; Pharmacology; Pharmacotherapy; Phenotype; Physicians; Pilot Projects; Plasma; Play; Prevention; Principal Investigator; Process; Proteins; Proteomics; Public Health; Reaction; Research; Resources; Role; Sampling; Science; Screening procedure; Selective Serotonin Reuptake Inhibitor; Series; Spectrometry; System; Techniques; Technology; Testing; Therapeutic; Tissues; Translating; United States National Institutes of Health; Validation; Variant; Washington; Wisconsin; base; cardiovascular disorder risk; clinical practice; drug development; drug discovery; drug mechanism; drug metabolism; functional genomics; human disease; human subject; member; metabolomics; microbiome; neuropsychiatry; organizational structure; prevent; protein expression; public health relevance; repository; response; small molecule; tool; transcriptomics; virtual

DESCRIPTION (provided by applicant): This proposal represents a response to Program Announcement PAR-07-412 "Preapplication for Large- Scale Collaborative Project Award ". The applicants propose to create an interdisciplinary research consortium with the goal of integrating the rapidly evolving science of metabolomics with molecular pharmacology and pharmacogenomics to move toward the creation of a new discipline - "Pharmacometabolomics" a discipline that will transform our ability to individualize therapy. Specifically, we propose the formation of a multi-institution research consortium involving centers of excellence in metabolomics and metabolomic bioinformatics, joined with centers of excellence in molecular pharmacology and pharmacogenomic science. The purpose is to create an environment in which a cooperative iterative process of hypothesis generation, testing, and validation will be applied to achieve the union of metabolomic and pharmacologic science to create "Pharmacometabolomics". Achievement of that goal would have the potential to dramatically accelerate advances in our understanding of mechanisms of disease, drug action, and variation in response to therapy. It would provide a treating physician with knowledge and biomarkers that can reduce an inadequate trial-and-error process in selecting the right drug for each patient. Through a partnership with members of the Pharmacogenetics Research Network and leveraging large investments already made by NIH we plan to employ metabolomic analyses to study drug response phenotypes by using prototypic drugs used to treat cardiovascular and neuropsychiatric disease as "testbeds" for the development and application of Pharmacometabolomics. That process will generate broadly based, biochemically precise "metabolomic signatures" to complement and extend the clinical response phenotypes currently being used to select drugs and monitor drug therapy and also to complement and extend genomic, transcriptomic and proteomic information with regard to drug response. This process would result in the generation of new hypotheses that will be tested in experimental animal and cultured cell systems - leading, in turn, to new translational hypotheses to which metabolomic analyses could also be applied. The ultimate goal of the proposed research consortium would be the creation of an environment in which it will be possible to develop Pharmacometabolomics as a truly "interdisciplinary" biomedical discipline that can contribute to a "Systems Pharmacology" approach to the study of drug effects leading to a more personalized approach to therapy. PUBLIC HEALTH RELEVANCE: Pharmacometabolomics is the application of metabolomic science to understand drug effect and variation in drug response phenotypes. A "Therapeutic Revolution" has transformed modern drug therapy. Therefore, it is increasingly important that we understand which patients might best respond to drug therapy without suffering adverse drug reactions. Creation of the Pharmacometabolomics Research Network proposed in this application would have a significant public health impact by helping make it possible to better understand and individualize drug therapy.

描述（由申请人提供）：该提案代表了对计划公告的回应PAR-07-412“大规模协作项目奖的预贴”。申请人建议建立一个跨学科研究联盟，目的是将快速发展的代谢组学科学与分子药理学和药物基因组学和药物基因组学融为一体，以朝着创建一项新学科的“ PharmacoCometabolomics”迈向一门学科，这将改变我们的个性化治疗能力。具体而言，我们提出了一个多机构研究联盟的形成，该联盟涉及代谢组学和代谢组生物信息学的卓越中心，并与分子药理学和药物基础科学的卓越中心一起。目的是创建一个环境，在这种环境中，将应用假设，测试和验证的合作迭代过程，以实现代谢组和药理学的结合以创建“药物代谢组学”。实现这一目标将有可能在我们对疾病，药物作用和对治疗的差异方面的理解中显着加速进步。它将为治疗医师提供知识和生物标志物，从而减少对每个患者选择合适的药物的反复试验过程不足。通过与药物遗传学研究网络成员的合作关系，并利用NIH已经进行的大量投资，我们计划采用代谢组学分析来研究药物反应表型，通过使用用于将心理和神经精神病的原型药物作为“测试床”的开发和应用，以开发和应用药物疾病。该过程将产生广泛基于生化精确的“代谢组学特征”，以补充和扩展当前用于选择药物并监测药物治疗的临床反应表型，并补充和补充和扩展基因组，转录和蛋白质组学信息。这个过程将导致产生新的假设，这些假设将在实验动物和培养的细胞系统中进行测试 - 进而导致新的转化假设，也可以应用代谢组分分析。拟议的研究联盟的最终目标是建立一个环境，在这种环境中，将有可能将药物代谢组学作为一种真正的“跨学科”生物医学纪律，该学科可以为“系统药理学”的方法进行研究，从而导致药物效应，从而导致一种更个性化的治疗方法。 公共卫生相关性：药物代谢组学是代谢组学在了解药物反应表型中的药物效应和变化的应用。 “治疗革命”改变了现代药物疗法。因此，越来越重要的是，我们了解哪些患者可能会在没有不良药物反应的情况下对药物治疗做出最好的反应。在本应用程序中提出的药物代谢组学研究网络的创建将通过帮助更好地理解和个性化药物疗法来产生重大的公共卫生影响。