Targeted and global proteomic strategies for early breast cancer detection

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Project Title: Targeted and global proteomic strategies for early breast cancer detection
Project Number: 5U24CA126477-03
Project web address: Follow on NIH
 
Project Description:
We propose to work cooperatively with other investigators funded by this U24 mechanism to evaluate proteomic technologies that will enable the early detection of several tumor types through the application of blood-based tests. Our group, consisting of scientists at LBNL, UCSF, The Buck Institute, MD Anderson Hospital, and the University of British Columbia, has the broad expertise that this project requires. We will focus on breast cancer. Initially, we will examine both global strategies and targeted mass spectrometry (MS)-based approaches to develop optimal workflows for the identification of protein signatures of human breast cancer cells in murine plasma. The global strategies will utilize multiple workflows that emphasize quantitative comparisons. The targeted approaches will focus on cancer-specific proteins that result from aberrant RNA splicing. Candidate biomarkers will be validated using reverse phase protein arrays. The requisite antibodies will be generated by Epitomics. The next phase of the project will employ human clinical samples. Specifically, we will apply an analogous, optimized approach for analyzing plasma samples that will be prospectively collected from breast cancer patients (n = 200). Control samples will be obtained from healthy women with benign breast disease and from women with rheumatoid arthritis to account for the contribution of proteins associated with inflammatory processes. Our candidate approach targets both the spliceome, which will be profiled using breast cancer biopsies from the plasma donors, and posttranslational modifications (e.g., glycosylation, phosphorylation, proteolysis and oxidative damage). We also include a plan for establishing a systematic way to standardize proteomic protocols and data analysis among the groups that exploits curability to analyze mass spectra generated on numerous platforms and the robust statistical methods we will employ to mine these large data sets. Several other elements of the RFA are also addressed. For example, we summarize the analysis capacity of our instruments and our strategy for sharing project-generated resources including biological specimens, protocols, data, software tools, and intellectual resources. In the end, we envision that our group, in conjunction with the other CPTAC teams and the NCI, will develop methods, tools and reference samples for the research community that will make the promise of MS-based cancer biomarker discovery a reality.
 
Project Terms:
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Project Title: Targeted and global proteomic strategies for early breast cancer detection
Project Number: 5U24CA126477-03
Project web address: Follow on NIH
Organization: University Of California San Francisco, United States, California, SAN FRANCISCO
Principal Investigators (PI): Fisher Susan J, US
 
Project Categories:
Natural Sciences > Aging Diseases and Pathology > Cancer & related diseases > Malignant neoplasms (including in situ) > Breast Cancer > Breast cancer, biomarkers, Breast cancer, treatment
 
Other Information:
Fiscal Year: 2006
Project Start Date: 28 September 2006
Project End Date: 31 August 2011
Project program: Resource-Related Research Projects--Cooperative Agreements
 
Project Funding Information:
Funding Mechanism: Cooperative agreements
Year Funding Organization Total Funding, $
2007 NIH - National Cancer Institute $1,539,272
Project Title: Targeted and global proteomic strategies for early breast cancer detection
Project Number: 5U24CA126477-03
Project web address: Follow on NIH
 
Title FY Funding
There are no results for this project in database.
Project Title: Targeted and global proteomic strategies for early breast cancer detection
Project Number: 5U24CA126477-03
Project web address: Follow on NIH
 
Title Journal Year Country Rel
Decoupling of the PI3K Pathway via Mutation Necessitates Combinatorial Treatment in HER2+ Breast Cancer. PLoS One 2015 united states
Variation and quantification among a target set of phosphopeptides in human plasma by multiple reaction monitoring and SWATH-MS2 data-independent acquisition. Electrophoresis 2014 germany
Coordinate phosphorylation of multiple residues on single AKT1 and AKT2 molecules. Oncogene 2014 england
Do breast cancer cell lines provide a relevant model of the patient tumor methylome? PLoS One 2014 united states
Phosphoprotein secretome of tumor cells as a source of candidates for breast cancer biomarkers in plasma. Mol Cell Proteomics 2014 united states
Identification and quantification of AKT isoforms and phosphoforms in breast cancer using a novel nanofluidic immunoassay. Mol Cell Proteomics 2013 united states
Breaking the bottleneck in the protein biomarker pipeline. Clin Chem 2012 united states
Lectin chromatography/mass spectrometry discovery workflow identifies putative biomarkers of aggressive breast cancers. J Proteome Res 2012 united states
RNA helicase DDX5 regulates microRNA expression and contributes to cytoskeletal reorganization in basal breast cancer cells. Mol Cell Proteomics 2012 united states
Platform-independent and label-free quantitation of proteomic data using MS1 extracted ion chromatograms in skyline: application to protein acetylation and phosphorylation. Mol Cell Proteomics 2012 united states
QuaMeter: multivendor performance metrics for LC-MS/MS proteomics instrumentation. Anal Chem 2012 united states
'Omic approaches to preventing or managing metastatic breast cancer. Breast Cancer Res 2011 england
Confident identification of 3-nitrotyrosine modifications in mass spectral data across multiple mass spectrometry platforms. J Proteomics 2011 netherlands
A lectin affinity workflow targeting glycosite-specific, cancer-related carbohydrate structures in trypsin-digested human plasma. Anal Biochem 2011 united states
Exon-level microarray analyses identify alternative splicing programs in breast cancer. Mol Cancer Res 2010 united states
Repeatability and reproducibility in proteomic identifications by liquid chromatography-tandem mass spectrometry. J Proteome Res 2010 united states
Performance metrics for liquid chromatography-tandem mass spectrometry systems in proteomics analyses. Mol Cell Proteomics 2010 united states
Interlaboratory study characterizing a yeast performance standard for benchmarking LC-MS platform performance. Mol Cell Proteomics 2010 united states
Sweetening the pot: adding glycosylation to the biomarker discovery equation. Clin Chem 2010 united states
A lectin HPLC method to enrich selectively-glycosylated peptides from complex biological samples. J Vis Exp 2009 united states
Acid-catalyzed oxygen-18 labeling of peptides. Anal Chem 2009 united states
IDPicker 2.0: Improved protein assembly with high discrimination peptide identification filtering. J Proteome Res 2009 united states
Yin yang 1 modulates taxane response in epithelial ovarian cancer. Mol Cancer Res 2009 united states
LARG at chromosome 11q23 has functional characteristics of a tumor suppressor in human breast and colorectal cancer. Oncogene 2009 england
Implementation of a data repository-driven approach for targeted proteomics experiments by multiple reaction monitoring. J Proteomics 2009 netherlands
RPPAML/RIMS: a metadata format and an information management system for reverse phase protein arrays. BMC Bioinformatics 2008 england
Validation of reverse phase protein array for practical screening of potential biomarkers in serum and plasma: accurate detection of CA19-9 levels in pancreatic cancer. Proteomics 2008 germany
A sequence-based survey of the complex structural organization of tumor genomes. Genome Biol 2008 england
A mass spectrometry-based strategy for detecting and characterizing endogenous proteinase activities in complex biological samples. Proteomics 2008 germany
Determining the overall merit of protein identification data sets: rho-diagrams and rho-scores. J Proteome Res 2007 united states
Non-parametric quantification of protein lysate arrays. Bioinformatics 2007 england
Project Title: Targeted and global proteomic strategies for early breast cancer detection
Project Number: 5U24CA126477-03
Project web address: Follow on NIH
 
Title Year
Project Title: Targeted and global proteomic strategies for early breast cancer detection
Project Number: 5U24CA126477-03
Project web address: Follow on NIH
 
Title Phase Year