Appl Of Microarray Tech To Understanding The Mechanism Of Environmental Agents

应用微阵列技术了解环境因素的作用机制

• 批准号: 8734056
• 负责人: Richard Paules
• 金额: $ 14.06万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8734056
• 关键词: Acetaminophen; Address; Adverse effects; Bioinformatics; Biological; Biological Markers; Biological Process; Blood; Blood Cells; Blood Circulation; Cells; Clinical; Disease; Dose; Environmental Exposure; Etiology; Excretory function; Exposure to; Gene Expression; Gene Expression Alteration; Genes; Genomics; Goals; Health; Human; Individual; Injury; Injury to Liver; Kidney; Liver; Malignant Neoplasms; Modeling; Molecular; Organ; Pathology; Process; Research Design; Rodent; Role; Stress; Testing; Time; Toxic Environmental Substances; Toxic effect; Toxicogenomics; Xenobiotics; base; design; environmental agent; follow-up; in vivo; insight; research study; response

This project of the Environmental Stress and Cancer Group investigates the molecular mechanisms of responses to environmental stresses involved in the etiology and progression of injury and disease processes. The overall goal of these studies is to provide a better understanding of the regulatory networks that control critical cellular responses to environmental stresses. Our approach utilizes advances in genomics and bioinformatics to address critical threats to human health as a consequence of environmental exposures. Specifically, the group is designing, executing, and analyzing studies that integrate global "omics" approaches with conventional studies of environmental stress, toxicity and disease processes. Core to these toxicogenomic efforts is the concept of phenotypic anchoring, in which studies are designed to relate alterations in gene expression to adverse effects defined by conventional parameters of toxicity and pathology. Studies are designed to provide insight into mechanisms of injury and disease as well as to establish signatures of adverse effects to develop putative biomarkers. These studies have utilized agents at multiple doses and times of treatment to fully explore ranges of biological responses to those agents. Analyses that implicate a critical role of a particular biological process or of a particular gene in an adverse response are followed up with additional experiments designed to test hypotheses concerning these roles. Studies have focused on the injury to the liver caused by exposures to a variety of hepatotoxic agents, including acetaminophen, and examined global gene expression changes in both the liver and circulating blood cells from rodents as well as blood cells from exposed humans for early indicators of the mechanism of injury as well as putative biomarkers.

环境压力和癌症小组的这个项目研究了对涉及损伤和疾病过程的病因学和进展的环境压力的反应的分子机制。这些研究的总体目标是更好地了解控制关键细胞对环境应激反应的调控网络。我们的方法利用基因组学和生物信息学的进步来解决环境暴露对人类健康的严重威胁。具体来说，该小组正在设计、执行和分析将全球“组学”方法与环境压力、毒性和疾病过程的传统研究相结合的研究。这些毒理基因组学工作的核心是表型锚定的概念，其中研究旨在将基因表达的改变与毒性和病理学常规参数定义的不良反应联系起来。研究旨在深入了解损伤和疾病的机制，并建立不良反应的特征，以开发推定的生物标志物。这些研究使用了多剂量和多次治疗的药物，以充分探索对这些药物的生物反应范围。分析牵连一个特定的生物过程或一个特定的基因在不良反应中的关键作用，随后进行额外的实验，旨在测试有关这些角色的假设。 研究集中于暴露于各种肝毒性剂（包括对乙酰氨基酚）引起的肝脏损伤，并检查了啮齿动物肝脏和循环血细胞以及暴露人类血细胞中的整体基因表达变化，以了解损伤机制的早期指标以及推定的生物标志物。

项目成果

Use of transcriptomics in understanding mechanisms of drug-induced toxicity.

• DOI: 10.2217/pgs.10.37
• 发表时间: 2010-04
• 期刊: Pharmacogenomics
• 影响因子: 2.1
• 作者: Cui Y;Paules RS
• 通讯作者: Paules RS

Moving forward in human cancer risk assessment.

• DOI: 10.1289/ehp.1002735
• 发表时间: 2011-06
• 期刊: Environmental health perspectives
• 影响因子: 10.4
• 作者: Paules RS;Aubrecht J;Corvi R;Garthoff B;Kleinjans JC
• 通讯作者: Kleinjans JC

Consistency of predictive signature genes and classifiers generated using different microarray platforms.

使用不同微阵列平台生成的预测特征基因和分类器的一致性

• DOI: 10.1038/tpj.2010.34
• 发表时间: 2010-08
• 期刊: The pharmacogenomics journal
• 作者: Fan X;Lobenhofer EK;Chen M;Shi W;Huang J;Luo J;Zhang J;Walker SJ;Chu TM;Li L;Wolfinger R;Bao W;Paules RS;Bushel PR;Li J;Shi T;Nikolskaya T;Nikolsky Y;Hong H;Deng Y;Cheng Y;Fang H;Shi L;Tong W
• 通讯作者: Tong W

Perturbation of microRNAs in rat heart during chronic doxorubicin treatment.

• DOI: 10.1371/journal.pone.0040395
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Vacchi-Suzzi C;Bauer Y;Berridge BR;Bongiovanni S;Gerrish K;Hamadeh HK;Letzkus M;Lyon J;Moggs J;Paules RS;Pognan F;Staedtler F;Vidgeon-Hart MP;Grenet O;Couttet P
• 通讯作者: Couttet P