APT: the Analytical Proteomics Team

APT：分析蛋白质组学团队

• 批准号: 7231865
• 负责人: Fred E Regnier
• 金额: $ 126.46万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-28 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7231865
• 关键词: biomarker; clinical research; human; mammary gland; neoplasm /cancer; prostate neoplasms; proteins; proteomics

DESCRIPTION (provided by applicant): Biomarker identification and characterization holds great promise for more precise diagnoses and for tailored therapies. The heterogeneity of human cancers and unmet medical needs in these diseases provides a compelling argument to focus biomarker development in cancer. Mass spectrometry (MS)-based proteomics approaches have provided insight into biomarkers of cancer and other diseases with femtomole sensitivity and high analytical precision, but the results have proven difficult to reproduce owing to the complexity of human biofluids and to the protocols employed in these approaches. This CPTAC proposal will develop robust protocols and standards for MS proteomics employing both electrospray ionization (ESI) and Matrix Assisted Laser Desorption Ionization (MALDI) platforms. Ion mobility MS provides several orders of magnitude increased dynamic range, and protocols for detection of cancer biomarker candidates will be further explored with this emerging technology platform. The consortium will employ high specificity immunologic reagents to develop platforms for precise detection and quantification of biomarkers of relevance for breast and prostate cancer. Immunoaffinity selection of specific biomarker proteins will be achieved as a sample fractionation step using nano-scale immunoaffinity columns prior to MS detection and quantification of specific proteins. An emerging technology incorporating specific antibodies on a microfabricated "bioCD" read by spinning disc interferometry enables label-free evaluation of hundreds of analytes from hundreds of samples in minutes. We will focus on candidate biomarkers relevant for breast and prostate cancer from the NF?B and STATS signaling pathways. Three for-profit and one not-for-profit corporate partners will join several academic groups with deep expertise and extensive resources in proteomics technologies to most efficiently evaluate and roll out robust protocols and standards for MS and affinity proteomics approaches. Prostate cancer samples will be made available from the NCI-sponsored ECOG trial; breast cancer patient and control samples will be collected specifically for this consortium by the Hoosier Oncology Group from throughout the State and region. Standardized sample collection organized from the Indiana University School of Medicine will ensure a diverse cross section of patient demographic groups. Three additional corporate partners will provide key technologies and consultation to improve team efficacy.

描述（由申请人提供）：生物标志物的识别和表征对于更精确的诊断和定制治疗具有巨大的希望。人类癌症的异质性和这些疾病中未满足的医疗需求为关注癌症生物标志物的开发提供了令人信服的论据。基于质谱 (MS) 的蛋白质组学方法以飞摩尔灵敏度和高分析精度深入了解癌症和其他疾病的生物标志物，但由于人类生物体液的复杂性以及这些方法中采用的方案，结果被证明难以重现。该 CPTAC 提案将为采用电喷雾电离 (ESI) 和基质辅助激光解吸电离 (MALDI) 平台的 MS 蛋白质组学开发强大的协议和标准。离子淌度 MS 提供了几个数量级的动态范围，并且将利用这一新兴技术平台进一步探索用于检测癌症生物标志物候选物的方案。该联盟将采用高特异性免疫试剂来开发用于精确检测和量化与乳腺癌和前列腺癌相关的生物标志物的平台。在 MS 检测和定量特定蛋白质之前，将使用纳米级免疫亲和柱作为样品分级步骤来实现特定生物标志物蛋白质的免疫亲和选择。一项新兴技术将特定抗体整合到微型“bioCD”上，通过旋转盘干涉测量法读取，可以在几分钟内对数百个样品中的数百种分析物进行无标记评估。我们将重点关注 NF?B 和 STATS 信号通路中与乳腺癌和前列腺癌相关的候选生物标志物。三个营利性和一个非营利性企业合作伙伴将加入多个在蛋白质组学技术方面拥有深厚专业知识和广泛资源的学术团体，以最有效地评估和推出针对 MS 和亲和蛋白质组学方法的稳健协议和标准。前列腺癌样本将从 NCI 赞助的 ECOG 试验中获得； Hoosier 肿瘤学小组将专门为该联盟从整个州和地区收集乳腺癌患者和对照样本。印第安纳大学医学院组织的标准化样本收集将确保患者人口群体的多样化。另外三个企业合作伙伴将提供关键技术和咨询，以提高团队效率。