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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Resource-Related Research Projects--Cooperative Agreements (U24)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-SRRB-C (O1))
Program Officer
Rodriguez, Henry
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Purdue University
Schools of Arts and Sciences
West Lafayette
United States
Zip Code
Zhang, Fan; Chen, Jake Y (2016) A method for identifying discriminative isoform-specific peptides for clinical proteomics application. BMC Genomics 17 Suppl 7:522
Kim, Jin-Hee; Inerowicz, Dorota; Hedrick, Vicki et al. (2013) Integrated sample preparation methodology for proteomics: analysis of native proteins. Anal Chem 85:8039-45
Zhang, Fan; Chen, Jake Y (2013) Breast cancer subtyping from plasma proteins. BMC Med Genomics 6 Suppl 1:S6
Rivera-Burgos, Dinelia; Regnier, Fred E (2013) Disparities between immobilized enzyme and solution based digestion of transferrin with trypsin. J Sep Sci 36:454-60
Kim, Jin-Hee; Woenker, Timothy; Adamec, Jiri et al. (2013) Simple, miniaturized blood plasma extraction method. Anal Chem 85:11501-8
Zhang, Fan; Wang, Mu; Michael, Tran et al. (2013) Novel alternative splicing isoform biomarkers identification from high-throughput plasma proteomics profiling of breast cancer. BMC Syst Biol 7 Suppl 5:S8
Ji, Chao; Arnold, Randy J; Sokoloski, Kevin J et al. (2013) Extending the coverage of spectral libraries: a neighbor-based approach to predicting intensities of peptide fragmentation spectra. Proteomics 13:756-65
Li, Yong Fuga; Radivojac, Predrag (2012) Computational approaches to protein inference in shotgun proteomics. BMC Bioinformatics 13 Suppl 16:S4
Rivera-Burgos, Dinelia; Regnier, Fred E (2012) Native protein proteolysis in an immobilized enzyme reactor as a function of temperature. Anal Chem 84:7021-8
Madian, Ashraf G; Hindupur, Jagadish; Hulleman, John D et al. (2012) Effect of single amino acid substitution on oxidative modifications of the Parkinson's disease-related protein, DJ-1. Mol Cell Proteomics 11:M111.010892

Showing the most recent 10 out of 45 publications