Functional Proteomics by Reverse Phase Protein Array in Cancer

癌症中反相蛋白阵列的功能蛋白质组学

• 批准号: 10251202
• 负责人: YILING LU
• 金额: $ 14.53万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-19 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10251202
• 关键词: Antibody Repertoire; Applications Grants; Atlases; Automation; Award; Biological Models; Cancer Center; Cancer Center Support Grant; Cells; Collaborations; Communities; Contractor; DNA sequencing; Data; Data Set; Disease; Drug Combinations; Ensure; Environment; Epigenetic Process; Funding; Generations; Genomics; International; Journals; Malignant Neoplasms; Medicine; Nature; New England; Paper; Patients; Peer Review Grants; Pharmacodynamics; Phase; Prognostic Marker; Protein Array; Proteins; Proteome; Proteomics; Publications; Research; Research Personnel; Resources; Sampling; Science; Services; Signal Pathway; Signal Transduction; Systems Biology; Technology; The Cancer Genome Atlas; Time; University of Texas M D Anderson Cancer Center; Visualization; Work; anticancer research; cBioPortal; career development; clinical application; cost effective; design; epigenomics; improved; interest; metabolomics; nano-string; neoplastic cell; predictive marker; professor; programs; protein function; response; single cell analysis; targeted cancer therapy; tumor

PROJECT SUMMARY Dr. Yiling Lu is a Research Non-Tenure-Track-Professor at University of Texas MD Anderson Cancer Center (MDACC) where she has served as a Core Manager of the CCSG Core of Functional Proteomics by Reverse Phase protein Array (RPPA). The Core is located in the Department of Systems Biology chaired by Dr. Gordon B Mills who acting as the Primary Unit Director in this award application. The RPPA Core provides MDACC investigators, their collaborators and the cancer research community with a powerful high throughput, quantitative, cost-effective technology for functional proteomics studies. The Core has analyzed more than 125,742 samples from 547 cancer researches across from the world over the last 8 years and supported for over 265 publications including high profile journals and more then 10 million dollars of peer-reviewed grant funding from the NCI and other agencies. The most significant evidence for the utility and robustness of the RPPA Core is that its inclusion in the Cancer Genome Atlas (TCGA) analysis for each disease type and its participation in over 25 of “pancan” “markers” papers in New England Journal of Medicine, Nature, Cell and Science and their clones. In addition to the generation of high quality RPPA data, one of the key aspects of the Core is the provision of functional proteomics data to the community. This is facilitated through the RPPA data being integrated into the cBioportal and being made available for downloading, analysis and visualization through The Cancer Proteome Atlas (TCPA portal). The RPPA contributions to progress in cancer research impact this scientific field around the world. Cancer targeted therapy is designed to capitalize on the vulnerabilities of tumor cells arising from the rewiring of functional networks as a consequence of the genomic and epigenetic changes in tumor or their effects on the tumor environment, impacting cellular protein functions. Thus, direct assessment of the targeted effects, both predicted and unexpected, on the key proteins in signaling networks is required. As clarified in this application, the facility will continue to provide RPPA services to MDACC investigators and the worldwide research community. 1) The facility will continue to expand the validated antibody repertoire to cover varies signaling pathways. 2) The facility will continue to improve the quality and accuracy of RPPA data sets. 3) The facility will continue to work with a contractor to build a RPPA pipeline automation program to decrease turnaround time. 4) The facility will develop the RPPA technology to maximize its applications for clinical usage. 5) The facility will develop single cell analysis through Nanostring technology and add it to functional proteomics service to meet the interests from investigators. To ensure the utility of the RPPA resource, Dr. Lu has multiple active collaborations at MDACC, as well as, nationally and internationally for her scientific activities and career development.

项目摘要 博士Yiling Lu是德克萨斯大学MD安德森癌症研究中心的非终身教授 中心（MDACC），她曾担任CCSG核心职能部门的核心经理 反相蛋白质阵列（RPPA）核心位于系统部 生物学由博士戈登B米尔斯谁担任主要单位主任在这个奖项的申请主持。 RPPA核心为MDACC研究者、他们的合作者和癌症研究社区提供了 具有强大的高通量、定量、经济高效的功能蛋白质组学技术， 问题研究The Core分析了来自547项癌症研究的超过125，742个样本， 在过去的8年里，我们支持了超过265种出版物，包括高知名度的期刊。 以及来自NCI和其他机构的超过1000万美元的同行评审拨款。的 RPPA核心的实用性和鲁棒性的最重要证据是， 癌症基因组图谱（TCGA）分析每种疾病类型及其参与超过25个 《新英格兰医学、自然、细胞和科学杂志》上的“泛参”“标记”论文及其对医学的影响 克隆除了生成高质量的RPPA数据外，Core的一个关键方面是 为社区提供功能蛋白质组学数据。这是通过RPPA数据提供的 被集成到cBioportal中，并可供下载、分析和 通过癌症蛋白质组图谱（TCPA门户）可视化。区域方案规划署对 癌症研究影响了全世界的科学领域。癌症靶向治疗旨在 利用肿瘤细胞因功能网络重新布线而产生的脆弱性， 肿瘤中基因组和表观遗传变化的结果或其对肿瘤的影响 环境，影响细胞蛋白质功能。因此，直接评估目标效果， 预测和意想不到的，对信号网络中的关键蛋白质是必需的。正如本文件所阐明的， 申请，该设施将继续提供RPPA服务，MDACC调查员和 全球研究界。1)该设施将继续扩大经验证的抗体库 以覆盖不同的信号通路。2)该设施将继续提高质量和准确性， RPPA数据集。3)该设施将继续与承包商合作，建造RPPA管道 自动化程序，以减少周转时间。4)该设施将开发RPPA技术， 最大限度地提高其临床应用。5)该设施将开发单细胞分析， Nanostring技术，并将其添加到功能蛋白质组学服务，以满足来自 investigators.为了确保RPPA资源的实用性，卢博士在 MDACC，以及，国内和国际为她的科学活动和职业发展。

项目成果

PIK-75 overcomes venetoclax resistance via blocking PI3K-AKT signaling and MCL-1 expression in mantle cell lymphoma.

• 发表时间: 2022
• 期刊: American journal of cancer research
• 影响因子: 5.3
• 作者: Shengjian Huang;Yang Liu;Zhihong Chen;Michael Wang;V. Jiang

Proteomic analysis of circulating extracellular vesicles identifies potential markers of breast cancer progression, recurrence, and response.

• DOI: 10.1126/sciadv.aba5714
• 发表时间: 2020-10
• 期刊: Science advances
• 影响因子: 13.6
• 作者: Vinik Y;Ortega FG;Mills GB;Lu Y;Jurkowicz M;Halperin S;Aharoni M;Gutman M;Lev S
• 通讯作者: Lev S

Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype.

• DOI: 10.1038/s41467-018-04179-8
• 发表时间: 2018-05-03
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Oh SC;Sohn BH;Cheong JH;Kim SB;Lee JE;Park KC;Lee SH;Park JL;Park YY;Lee HS;Jang HJ;Park ES;Kim SC;Heo J;Chu IS;Jang YJ;Mok YJ;Jung W;Kim BH;Kim A;Cho JY;Lim JY;Hayashi Y;Song S;Elimova E;Estralla JS;Lee JH;Bhutani MS;Lu Y;Liu W;Lee J;Kang WK;Kim S;Noh SH;Mills GB;Kim SY;Ajani JA;Lee JS
• 通讯作者: Lee JS

The Role of GDF15 in Regulating the Canonical Pathways of the Tumor Microenvironment in Wild-Type p53 Ovarian Tumor and Its Response to Chemotherapy.

• DOI: 10.3390/cancers12103043
• 发表时间: 2020-10-19
• 期刊: Cancers
• 影响因子: 5.2
• 作者: Izaguirre DI;Ng CW;Kwan SY;Kun EH;Tsang YTM;Gershenson DM;Wong KK
• 通讯作者: Wong KK

Mechanical Stress Signaling in Pancreatic Cancer Cells Triggers p38 MAPK- and JNK-Dependent Cytoskeleton Remodeling and Promotes Cell Migration via Rac1/cdc42/Myosin II.

• DOI: 10.1158/1541-7786.mcr-21-0266
• 发表时间: 2022-03-01
• 期刊: Molecular cancer research : MCR
• 作者: Kalli M;Li R;Mills GB;Stylianopoulos T;Zervantonakis IK
• 通讯作者: Zervantonakis IK