Teams of the Alliance
Pierce Tumor Glycomics Laboratory
Principal Investigator: J. Michael Pierce, PhD
Institution: University of Georgia, Athens, GA
Our project, Discovery and Development of Cancer Glycomarkers, is a joint collaboration between our laboratories at the CCRC, which include Karen Abbott, Lance Wells, Kevin Dobbin, and Mike Tiemeyer, those at TGen, in Phoenix, AZ, Daniel Von Hoff, Haiyong Han, and Mike Demeure, and Caerus Discovery in Manassas, VA, which includes Cohava Gelber and S?ren Mogelsvang.
We have identified a novel N-glycan biomarker for pancreatic cancer defined by a suite of antibodies developed by Caerus Discovery. Screening >150 tissue sections by immunohistochemistry showed a high sensitivity and specificity for this marker in pancreatic carcinoma, even at early stages. Initial studies have detected the biomarker in serum from pancreatic cancer patients, suggesting that assays may be refined to develop it into a diagnostic test. Moreover, we are studying the glycomics and proteomics of stellate cells that are found tightly associated with pancreatic carcinoma and in many cases block chemotherapy from penetrating these tumors. These studies are likely to point to markers that can be used to develop additional molecular targets to aid in the diagnosis and treatment of pancreatic cancer.
In addition, we have identified a specific glycoform of periostin in tissues and in serum as a marker for invasive breast carcinoma. These tests are being expanded to screen large numbers of test and control sera to determine the efficacy of this serum marker. We have also developed a means to separate many GPI-anchored glycoproteins from serum and tissue. Two glycoproteins in serum associate with the presence of breast cancer. These biomarkers are being tested in sera from larger populations of patients and controls.
Many of our glycoproteomics technologies have been developed in our NIGMS National Center for Biomedical Glycomics at the Complex Carbohydrate Research Center, University of Georgia. We have state-of-the-art instrumentation and expertise to analyze glycan and glycopeptide structures and the expression of transcripts that regulate human glycans expression. The National Glycomics Center is focused on understanding the regulation of the glycome during embryonic stem cell, iPS cell, and cancer stem cell differentiation, as well as identifying potential cell surface biomarkers of these various cell types. Our National Center also has a vigorous analytical service program, and offers workshops on analysis of glycan structure: http://glycomics.ccrc.uga.edu.
- Porterfield M, Zhao P, Han H, Cunningham J, Aoki K, Von Hoff DD, Demeure MJ, Pierce JM, Tiemeyer M, Wells L. Discrimination between Adenocarcinoma and normal pancreatic ductal fluid by proteomic and glycomic analysis. J Proteome Res. 2014; 13(2):395-407.
- Cummings RD, Pierce JM. The challenge and promise of glycomics. Chem Biol. 2014; 21(1):1-15.
- Zhao P, Nairn AV, Hester S, Moremen KW, O'Regan RM, Oprea G, Wells L, Pierce M, Abbott KL. Proteomic identification of glycosylphosphatidylinositol anchor-dependent membrane proteins elevated in breast carcinoma. J Biol Chem. 2012; 287(30):25230-40.
- Guo H, Nairn A, Dela Rosa M, Nagy T, Zhao S, Moremen K, Pierce M. Transcriptional regulation of the protocadherin cluster during Her-2 protein-induced mammary tumorigenesis results from altered N-glycan branching. J Biol Chem. 2012; 287(30):24941-54.
- Langer MD, Guo H, Shashikanth N, Pierce JM, Leckband DE. N-glycosylation alters cadherin-mediated intercellular binding kinetics. J Cell Sci. 2012; 125(Pt 10):2478-85.
- Abbott KL, Pierce JM. Lectin-based glycoproteomic techniques for the enrichment and identification of potential biomarkers. Methods Enzymol. 2010; 480:461-76.
- Guo HB, Johnson H, Randolph M, Nagy T, Blalock R, Pierce M. Specific posttranslational modification regulates early events in mammary carcinoma formation. Proc Natl Acad Sci U S A. 2010; 107(49):21116-21
- Abbott KL, Lim JM, Wells L, Benigno BB, McDonald JF, Pierce M. Identification of candidate biomarkers with cancer-specific glycosylation in the tissue and serum of endometrioid ovarian cancer patients by glycoproteomic analysis. Proteomics. 2010; 10(3):470-81.
- Guo HB, Johnson H, Randolph M, Pierce M. Regulation of homotypic cell-cell adhesion by branched N-glycosylation of N-cadherin extracellular EC2 and EC3 domains. J Biol Chem. 2009; 284:34986-97.
- Abbott KL, Aoki K, Lim JM, Porterfield M, Johnson R, O'Regan RM, Wells L, Tiemeyer M, Pierce M. Targeted glycoproteomic identification of biomarkers for human breast carcinoma. J Proteome Res. 2008; 7(4):1470-80.
- Abbott KL, Nairn AV, Hall EM, Horton MB, McDonald JF, Moremen KW, Dinulescu DM, Pierce M. Focused glycomic analysis of the N-linked glycan biosynthetic pathway in ovarian cancer. Proteomics. 2008; 8(16): p. 3210-20.
- Pierce JM. "Cancer Glycomics" in Handbook of Glycomics. Ed R.D. Cummings, J.M. Pierce. Academic Press: 2009, San Diego. p. 399-430.
- Porterfield M, Zhao P, Han H, Cunningham J, Aoki K, Von Hoff DD, Demeure MJ, Pierce JM, Tiemeyer M, Wells L. Discrimination between adenocarcinoma and normal pancreatic ductal fluid by glycoproteomic analysis. J. Proteome Res. 2012; (in final review).
In the Media:
"Tracking a killer," Maximizing Research Opportunities,online feature, Aug 22, 2007.
Survivor a beacon in cancer research . Ken Foskett, Atlanta Journal-Constitution, Oct. 22, 2007.
Methods to Identify and Quantify Oligosaccharide Modifications of Glycoproteins (US 7,351,544).
Provisional Application: Glycoprotein Cancer Biomarkers Filed: June 11, 2010. (serial # 12/814,184).
Provisional Application: Cancer-specific Glycans and Glycopeptides Filed: July 13, 2010 (serial# 61/363,782).
Provisional Application: Alpha Toxin Detection of GPI Anchored Proteins Filed: August 6, 2010 (serial# 61/371,326).