Research Summary
Dr. Zhang studies protein modification on the proteome scale and the effects of modification on protein function and disease progression. For the past few years, her research has focused on the development of high-throughput technologies to isolate and identify two of the most abundant protein modifications - phosphorylation and glycosylation.
One technology enables capturing and identification of modified peptides using affinity chromatography. To do so, she has developed a group of antibodies reactive against a variety of protein modification sites, such as phosphorylation, nitration, acetylation, and substrates of a specific modification enzyme, etc. Among those, phospho-specific antibodies have enabled isolation of a large number of phosphorylated peptides that can be subsequently identified by tandem mass spectrometry.
A second technology enables capturing glycopeptides using solid phase extraction, which has become a powerful tool to analyze glycoproteins on cell surface and in body fluids. Thus far, thousands of novel glycosylation sites have been identified from different tissues using this novel glycopeptide capture technology; this significantly expends the limited number of glycosylation sites experimentally identified prior to the new technology.
These methods are highly sensitive, holding a strong promise for discovering low abundance disease marker proteins in tissue, plasma or other body fluids.
Currently, Dr. Zhang is applying these proteomics technologies to determine protein modifications associated with cancer, which well help for early detection and improved monitoring of therapeutic effects. She is also developing novel methods to study protein modifications that will have major implications for a wide range of health issues.
Technology Expertise Keywords
Proteomics; mass spectrometry; glycoproteimics; glycomics; phosphoproteomics
Selected Publications
Zhang H, Liu T, Zhang Z, Payne SH, Zhang B, McDermott JE, Zhou J, Petyuk VA, Chen L, Ray D, Sun S, Yang F, Chen L, Wang J, Shah P, Cha S-W, Aiyetan P, Woo S, Tian Y, Gritsenko MA, Choi C, Monroe ME, Thomas S, Moore RJ, ,Yu K-H, Tabb DL, Fenyö D, Bafna V, Wang Y, Rodriguez H, Boja ES, Hiltke T, Rivers RC, Sokoll L, Zhu H, Shih I-M, Pandey A, Zhang B, Snyder MP, Levine DA, Smith RD, Chan DW, Rodland KD, and the CPTAC investigators. Deep proteogenomic characterization of human ovarian cancer. Cell. 2016; 166: 755-765.
Sun S, Shah P, Toghi Eshghi S, Yang W, Trikannad N, Yang S, Chen L, Aiyetan P, Hoti NU, Zhang Z, Chan DW, Zhang H*. Comprehensive analysis of protein glycosylation by solid-phase extraction of N-linked glycans and glycosite-containing peptides. Nature Biotechnology. 2016; 34: 84-88.
Shah P, Wang X, Yang W, Toghi Eshghi S, Sun S, Hoti N, Pasay J, Rubin A, Zhang H*. Integrated proteomic and glycoproteomic analyses of prostate cancer cells reveals glycoprotein alteration in protein abundance and glycosylation. Molecular & Cellular Proteomics. 2015; 14: 2753-2763.
Toghi Eshghi S, Shah P, Yang W, Li X, Zhang H*. GPQuest: A Spectral Library Matching Algorithm for Site-Specific Assignment of Spectra from Tandem Mass Spectrometric Analysis of Intact Glycopeptides. Analytical Chemistry. 2015; 87: 5181-5188.
Zhang, H., Li, X. J., Martin, D. B., and Aebersold, R. Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nature Biotechnology (2003) 21:660.
Patents
Biomarkers for Prostate Cancer.
Patent # 8,603,734 | 2007
Production of Motif-Specific and Context-Independent Antibodies Using Peptide Libraries as Antigens
Patent # 7,259,022 | 2001
Immunoaffinity Isolation of Modified Peptides From Complex Mixtures
Patent # 7,198,896 | 2002
Methods for Quantitative Proteome Analysis of Glycoproteins
Patent # 7183118B2 | 2003
Affinity Capture Of Peptides By Microarray And Related Methods
Patent # 7,794,947 | 2003
