This project brings together researchers who have established research track records in high-throughput platforms of carbohydrate microarrays, neoglycolipid (NGL) technology coupled with mass spectrometry for carbohydrate ligand discovery, flow cytometry (Hi-D FACS) for highly-sensitive detection of cell and serum markers, and the first international standard for detection of prostate-specific antigen (PSA). The thrust of this team is identification and characterization of immunological biomarkers and development of highly sensitive assays for clinical and research applications. The ultimate goal of this project is to identify novel serum biomarkers for detection of prostate cancer and monitoring of cancer progression. In preliminary investigations, they have identified a number of carbohydrate-based biomarkers in prostate cancers. In addition, they have detected autoantibodies to some of these using carbohydrate microarrays. They hypothesize that these aberrantly expressed carbohydrates are immunogenic and are able to induce specific autoantibodies in prostate cancer subjects. Detection of such antibodies in serum could allow detection of prostate cancer and its aggressive progression. In this project, collaborating group plan to examine their hypotheses by characterizing a large-collection of well-categorized serum and tissue specimens preserved in their prostate cancer tissue banks. They plan to 1) determine whether anti-carbohydrate autoantibodies specific for Mannose-clusters and other A/-glycans not normally expressed can distinguish between men with BPH and prostate cancer and/or predict the aggressive and progressive prostate cancers;2) determine whether serum antibodies specific for other carbohydrate autoantigens are present in prostate cancer subjects and evaluate their diagnostic and prognostic values;3) determine whether the presence of certain anti-carbohydrate antibodies in the serum of an individual correlates with the aberrant expression of corresponding glyco-epitopes in the prostate cancer;4) determine the carbohydrate O-glycan sequences of glyco-epitopes of HCA and other cancer-associated glycoproteins that are recognized by mAb AE3 and G1;and 5) establish highly sensitive and user-friendly immunoassays using novel serological markers to facilitate a large-scale clinical study of prostate cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA128416-05
Application #
8125080
Study Section
Special Emphasis Panel (ZCA1-SRRB-4 (J1))
Program Officer
Krueger, Karl E
Project Start
2007-08-06
Project End
2014-06-30
Budget Start
2011-08-08
Budget End
2014-06-30
Support Year
5
Fiscal Year
2011
Total Cost
$427,463
Indirect Cost
Name
Sri International
Department
Type
DUNS #
009232752
City
Menlo Park
State
CA
Country
United States
Zip Code
94025
Jiang, Yi; Wang, Denong (2018) Liquid Biopsy in the OMICS Era of Tumor Medicine. Open Access J Biomed Eng Appl 1:
Liu, Yan; Palma, Angelina S; Feizi, Ten et al. (2018) Insights Into Glucan Polysaccharide Recognition Using Glucooligosaccharide Microarrays With Oxime-Linked Neoglycolipid Probes. Methods Enzymol 598:139-167
Wang, Denong (2017) Unraveling Sugar Chain Signatures of the ""Seeds"" of Tumor Metastasis. J Proteomics Bioinform 10:
Wang, Denong; Wu, Lisa; Liu, Xiaohe (2017) Glycan Markers as Potential Immunological Targets in Circulating Tumor Cells. Adv Exp Med Biol 994:275-284
Wang, Denong; Liu, Xiaohe; Hsieh, Ben et al. (2015) Exploring Glycan Markers for Immunotyping and Precision-targeting of Breast Circulating Tumor Cells. Arch Med Res 46:642-50
Wang, Denong; Tang, Jin; Tang, Jiulai et al. (2015) Targeting N-glycan cryptic sugar moieties for broad-spectrum virus neutralization: progress in identifying conserved molecular targets in viruses of distinct phylogenetic origins. Molecules 20:4610-22
Wang, Denong; Tang, Jin; Liu, Shaoyi et al. (2015) Carbohydrate Microarrays Identify Blood Group Precursor Cryptic Epitopes as Potential Immunological Targets of Breast Cancer. J Immunol Res 2015:510810
Falkowska, Emilia; Le, Khoa M; Ramos, Alejandra et al. (2014) Broadly neutralizing HIV antibodies define a glycan-dependent epitope on the prefusion conformation of gp41 on cleaved envelope trimers. Immunity 40:657-68
Gao, Chao; Liu, Yan; Zhang, Hongtao et al. (2014) Carbohydrate sequence of the prostate cancer-associated antigen F77 assigned by a mucin O-glycome designer array. J Biol Chem 289:16462-77
Palma, Angelina S; Feizi, Ten; Childs, Robert A et al. (2014) The neoglycolipid (NGL)-based oligosaccharide microarray system poised to decipher the meta-glycome. Curr Opin Chem Biol 18:87-94

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