Nanosystems Biology Cancer Center 2

纳米系统生物学癌症中心 2

• 批准号: 8707986
• 负责人: James R. Heath
• 金额: $ 235.75万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-03 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8707986
• 关键词: Biology; Cancer Center; nanosystems

Organ-specific, blood protein biomarkers for an informative diagnosis of brain and ovarian cancers: technologies for rapid evaluation, validation, and clinical translation Abstract. Our first hypothesis is that organ-specific, secreted biomarkers constitute a molecular fingerprint of the biological networks in each organ. These proteins can change during the progression from health to disease and disease treatment, and provide information relevant to early diagnosis, disease stratification and progression, and therapy response. These markers provide an exciting opportunity for brain and ovarian cancer diagnostics. Our second hypothesis is that highly multiplexed measurements of serum-based protein biomarkers will become a routine clinical tool only if those measurements are quantitative, highly sensitive, and inexpensive. These two hypotheses drive the biology and technology within this project. We describe a blood protein biomarker discovery and validation pathway, as applied to qlioblastoma multiforme (GBM) and ovarian cancer. The pathway begins with the identification of potential organ-specific blood proteins via comparative deep transcriptome analysis, coupled with a search of extant blood protein databases. These biomarkers are pre-validated using unique mass spectrometric methods applied to mouse models and human sera. The most promising markers are translated onto a chip for large scale validation on cancer patients via analysis of a pinprick of blood. The fourth step is to replace the most expensive aspect of those measurements (the antibodies) with a more stable but equal performance alternative. Two nanotechnologies enable this approach. They are protein click-catalyzed capture agents (PCC agents), which are highly modular, chemically synthesized protein capture agents that are assembled by the protein target itself. PCC agents can exhibit the affinity and selectivity of antibodies, but also (bio)chemical and physical stability - thus permitting the routine use of highly multiplexed protein assays. The second nanotechnology permits the routine counting of individual, specific protein molecules, thus extending the sensitivity of multiplexed protein assays by orders of magnitude (and thus to small organs).

用于脑癌和卵巢癌诊断的器官特异性血液蛋白生物标志物：

项目成果

An integrated microfluidic chip system for single-cell secretion profiling of rare circulating tumor cells.

用于稀有循环肿瘤细胞单细胞分泌分析的集成微流控芯片系统

• DOI: 10.1038/srep07499
• 发表时间: 2014-12-16
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Deng Y;Zhang Y;Sun S;Wang Z;Wang M;Yu B;Czajkowsky DM;Liu B;Li Y;Wei W;Shi Q
• 通讯作者: Shi Q

A protein-targeting strategy used to develop a selective inhibitor of the E17K point mutation in the PH domain of Akt1.

• DOI: 10.1038/nchem.2223
• 发表时间: 2015-05
• 期刊: Nature chemistry
• 影响因子: 21.8

Epitope targeting of tertiary protein structure enables target-guided synthesis of a potent in-cell inhibitor of botulinum neurotoxin.

• DOI: 10.1002/anie.201502451
• 发表时间: 2015-06-08
• 期刊: Angewandte Chemie (International ed. in English)
• 作者: Farrow B;Wong M;Malette J;Lai B;Deyle KM;Das S;Nag A;Agnew HD;Heath JR
• 通讯作者: Heath JR

Accurate dispensing of volatile reagents on demand for chemical reactions in EWOD chips.

• DOI: 10.1039/c2lc40244k
• 发表时间: 2012-09-21
• 期刊: Lab on a chip
• 影响因子: 6.1
• 作者: Ding H;Sadeghi S;Shah GJ;Chen S;Keng PY;Kim CJ;van Dam RM
• 通讯作者: van Dam RM

Electrochemical nucleophilic synthesis of di-tert-butyl-(4-[18F]fluoro-1,2-phenylene)-dicarbonate.

• DOI: 10.1016/j.apradiso.2014.06.013
• 发表时间: 2014-09
• 期刊: Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine
• 作者: He Q;Wang Y;Alfeazi I;Sadeghi S
• 通讯作者: Sadeghi S