Cancer biology and diagnostics
Our work in Cancer Biology and Diagnostics began with the founding of the Ayers Institute in 2006. The mission of the Ayers Institute is to develop new cancer diagnostics, with an initial focus on the early detection of colorectal cancer. We established a biomarker development pipeline based on standardized technology platforms that were developed over the past 5 years, in part through our participation as one of 5 centers in the first phase of the NCI Clinical Proteomic Technology Assessment for Cancer program (2006-2011).
Our most recent work demonstrates the maturity of our analysis platforms.
- A standardized shotgun proteomics platform characterized proteomic differences between colon tumor cells differing by expression of a single mutant gene.
- The shotgun analysis platform, coupled with new informatics tools, can identify protein variants encoded by cancer-related mutations.
- Multiplexed MRM assays can quantify groups of proteins associated with cancer phenotypes and responses to targeted therapeutics.
- Shotgun and MRM proteomic analyses can be applied to analyze archival formalin-fixed, paraffin-embedded (FFPE) tissue specimens with results equivalent to those for analyses of frozen tissues.
These platforms are being implemented in two major NCI-funded projects. The first is the Vanderbilt Biomarker Developmental Laboratory, which is funded by the NCI Early Detection Research Network (EDRN). Our program is focused on development and early stage validation of protein expression biomarkers for lng, colon and pancreatic cancers.
The second program is the Vanderbilt Proteome Characterization Center, which is funded as part of the NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC). This network is analyzing tumor tissues also analyzed by the NCI Cancer Genome Atlas (TCGA) program, which is generating comprehensive genomic characterization. Proteomic analyses by the CPTAC network will bridge the gap between genomic features and cancer phenotypes and we expect work on this project over the next 5 years will fundamentally advance our understanding of cancer biology.
Sprung, R. W., Jr., Brock, J. W., Tanksley, J. P., Li, M., Washington, M. K., Slebos, R. J., and Liebler, D. C. (2009) Equivalence of protein inventories obtained from formalin-fixed paraffin-embedded and frozen tissue in multidimensional liquid chromatography-tandem mass spectrometry shotgun proteomic analysis. Mol Cell Proteomics, 8, 1988-1998. PubMed
Li, M., Gray, W., Zhang, H., Chung, C. H., Billheimer, D., Yarbrough, W. G., Liebler, D. C., Shyr, Y., and Slebos, R. J. (2010) Comparative shotgun proteomics using spectral count data and quasi-likelihood modeling. J. Proteome Res., 9, 4295-4305. PubMed
Li, J., Su, Z., Ma, Z. Q., Slebos, R. J., Halvey, P., Tabb, D. L., Liebler, D. C., Pao, W., and Zhang, B. (2011) A bioinformatics workflow for variant peptide detection in shotgun proteomics. Mol Cell Proteomics, 10, M110 006536. PubMed
Halvey, P. J., Zhang, B., Coffey, R. J., Liebler, D. C., and Slebos, R. J. (2012) Proteomic consequences of a single gene mutation in a colorectal cancer model. J. Proteome Res., 11, 1184-1195. PubMed
Myers, M. V., Manning, H. C., Coffey, R. J., and Liebler, D. C. (2012) Protein Expression Signatures for Inhibition of Epidermal Growth Factor Receptor-mediated Signaling. Mol Cell Proteomics, 11, M111 015222. PubMed