Hollingsworth Tumor Glycomics Laboratory
Principal Investigator: Michael Hollingsworth, Ph.D.
Institution: University of Nebraska, Omaha, NE
The Hollingsworth Tumor Glycomics Laboratory focuses on pancreatic cancer and other diseases of the pancreas, primarily pancreatitis. Using cutting-edge technologies in molecular biology, biochemistry, cell biology, and immunology, this laboratory is developing a comprehensive program to investigate the biology of normal and diseased pancreatic ductal epithelial cells.
The laboratory's goal is to develop unique microarray-based assays to detect auto-antibodies to glycopeptide epitopes of glycoproteins, and to evaluate their usefulness as diagnostic biomarkers for early detection of pancreatic cancer as well as adenocarcinomas derived from other organ sites. They are also examining the expression of tumor-associated glycan structures and mucin core proteins in tissues of patients with early and late stage pancreatic cancer.
Specific aims include: characterize the specificities of auto-antibodies using novel arrays for screening sera ed. from pancreatic cancer patients, and serial samples of sera taken before diagnosis of pancreatic and other carcinomas; document the expression of mucins from early stage pancreatic cancer to invasive and metastatic disease, and correlate underglycosylation with the presence or absence of autoantibody responses; and characterize expression of tumor associated glycans and glycosyltransferases in metastatic pancreatic cancer using a series of cases for which they have primary tumor and multiple metastatic sites obtained by rapid autopsy.
Core facilities at the laboratory include cell culture, mutagenesis, nuclear magnetic resonance, mass spectrometry, histology, animal care, electron microscopy, phosphorimager, monoclonal antibody production, DNA sequencing, oligonucleotide production, capillary electrophoresis, 2-dimensional gel electrophoresis and analysis, microarray production and analysis, microscopy, high throughput screening, and large-scale production of recombinant products.
Publications:
- Blixt O, Bueti D, Burford B, Allen D, Julien S, Hollingsworth M, Gammerman A, Fentiman I, Taylor-Papadimitriou J, Burchell JM. Autoantibodies to aberrantly glycosylated MUC1 in early stage breast cancer are associated with a better prognosis. Breast Cancer Res. 2011; 13(2):R25. [Epub ahead of print]
- Kracun SK, Cló E, Clausen H, Levery SB, Jensen KJ, Blixt O. Random glycopeptide bead libraries for seromic biomarker discovery. J Proteome Res. 2010; 9(12):6705-14.
- Blixt O, Cló E, Nudelman AS, Sørensen KK, Clausen T, Wandall HH, Livingston PO, Clausen H, Jensen KJ. A high-throughput O-glycopeptide discovery platform for seromic profiling. J Proteome Res. 2010; 9(10):5250-61. Erratum in: J Proteome Res. 2011 10(3):1436.
- Wandall HH, Blixt O, Tarp MA, Pedersen JW, Bennett EP, Mandel U, Ragupathi G, Livingston PO, Hollingsworth MA, Taylor-Papadimitriou J, Burchell J, Clausen H. Cancer biomarkers defined by autoantibody signatures to aberrant O-glycopeptide epitopes. Cancer Res. 2010; 70(4):1306-13.
- Yue T, Goldstein IJ, Hollingsworth MA, Kaul K, Brand RE, Haab BB. The prevalence and nature of glycan alterations on specific proteins in pancreatic cancer patients revealed using antibody-lectin sandwich arrays. Mol Cell Proteomics. 2009; 8(7):1697-707.
- Costa NR, Mendes N, Marcos NT, Reis CA, Caffrey T, Hollingsworth MA, Santos-Silva F. Relevance of MUC1 mucin variable number of tandem repeats polymorphism in H pylori adhesion to gastric epithelial cells. World J Gastroenterol. 2008;14(9):1411-4.
- Wandall HH, Irazoqui F, Tarp MA, Bennett EP, Mandel U, Takeuchi H, Kato K, Irimura T, Suryanarayanan G, Hollingsworth MA, Clausen H. The lectin domains of polypeptide GalNAc-transferases exhibit carbohydrate-binding specificity for GalNAc: lectin binding to GalNAc-glycopeptide substrates is required for high density GalNAc-O-glycosylation. Glycobiology. 2007; 17(4):374-87.
- Swanson BJ, McDermott KM, Singh PK, Eggers JP, Crocker PR, Hollingsworth MA. MUC1 is a counter-receptor for myelin-associated glycoprotein (siglec-4a) and their interaction contributes to adhesion in pancreatic cancer perineural invasion. Cancer Res. 2007; 67(21):10222-9.
In the Media:
"Antibodies Against Abnormal Glycoproteins Identified as Possible Biomarkers for Cancer Detection", NCI Press Release, February 2, 2010
"Race against time. UNMC researchers to improve odds for patients with pancreatic cancer," UNMC Website, Nov. 12, 2009.
"Researchers to raise cancer awareness over 140 miles," UNMC Today, Intranet, October 29, 2008.
"Meet Distinguished Scientist Tony Hollingsworth, Ph.D.," UNMC Today, Intranet, February 21, 2007.
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