This proposal describes a research development plan in cancer studies for the candidate. The proposal includes a research plan, which aims to address pressing issues in developing early diagnosis of pancreatic cancer;and a training plan, which will provide comprehensive training emphasizing on clinical research and cancer biology for the candidate. The mentoring team for this proposal represents outstanding expertise and many years of clinical and research experience in pancreatic cancer, molecular biology, proteomics and biomarker development. The proposed research is to investigate dysregulated glycosylations in pancreatic cancer. Pancreatic cancer is a highly lethal disease that is very difficult to diagnosis and treat. One of the major obstacles for improving the outcome in this highly aggressive tumor arises from the difficulty in diagnosing the disease at an early stage, a goal that could markedly improve the survival rate. Abnormal glycosylation of proteins is often associated with malignant transformation, leading to the accumulation of tumor-specific glycoproteins actively involved in tumor progression and metastasis. In the area of pancreatic cancer studies, little information is available describing the glycoproteome present in normal pancreas, and even less in pancreatic cancer. A systematic investigation of glycoproteins in associated with pancreatic cancer can lead to identification of biomarkers and better understanding of glycosylation process implicated with pancreatic cancer. This is an important area that remains largely unexplored and could provide a gold mine of clinically valuable information. The proposed study is to identify dysregulated glycoproteins associated with pancreatic cancer using a platform technology integrating glycoprotein enrichment techniques and mass spectrometry based quantitative proteomics. The study will further validate and investigate the dysregulated glycoproteins to reveal their roles in the development of pancreatic cancer for early diagnosis and therapeutic targets. The successful completion of this proposal will provide a better understanding of the glycosylation events that underlie pancreatic cancer and may ultimately lead to biomarkers for early diagnosis or therapeutic target. In addition, it will launch the candidate to be an independent biomedical researcher.

Public Health Relevance

Pancreatic cancer is the fourth leading cause of cancer death in the United State and it is very difficult to diagnosis at an early stage when the disease is curable. Abnormal glycosylation can be a hallmark of pancreatic cancer. A systematic investigation of aberrant glycoproteins associated with pancreatic cancer will provide a better understanding of the glycosylation events that underlie pancreatic cancer and may ultimately lead to biomarkers for early diagnosis or therapeutic target.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Mentored Quantitative Research Career Development Award (K25)
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Subcommittee G - Education (NCI)
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Jakowlew, Sonia B
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University of Washington
Schools of Medicine
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Pan, Sheng; Chen, Ru; Tamura, Yasuko et al. (2014) Quantitative glycoproteomics analysis reveals changes in N-glycosylation level associated with pancreatic ductal adenocarcinoma. J Proteome Res 13:1293-306
Pan, Sheng (2014) Quantitative glycoproteomics for N-glycoproteome profiling. Methods Mol Biol 1156:379-88
Pan, Sheng; Brentnall, Teresa A; Kelly, Kimberly et al. (2013) Tissue proteomics in pancreatic cancer study: discovery, emerging technologies, and challenges. Proteomics 13:710-21
Pan, Sheng; Chen, Ru; Brand, Randall E et al. (2012) Multiplex targeted proteomic assay for biomarker detection in plasma: a pancreatic cancer biomarker case study. J Proteome Res 11:1937-48
Pan, Sheng; Chen, Ru; Stevens, Tyler et al. (2011) Proteomics portrait of archival lesions of chronic pancreatitis. PLoS One 6:e27574
Pan, Sheng; Chen, Ru; Aebersold, Ruedi et al. (2011) Mass spectrometry based glycoproteomics--from a proteomics perspective. Mol Cell Proteomics 10:R110.003251
Pan, Sheng; Chen, Ru; Crispin, David A et al. (2011) Protein alterations associated with pancreatic cancer and chronic pancreatitis found in human plasma using global quantitative proteomics profiling. J Proteome Res 10:2359-76
Chen, Ru; Pan, Sheng; Duan, Xiaobo et al. (2010) Elevated level of anterior gradient-2 in pancreatic juice from patients with pre-malignant pancreatic neoplasia. Mol Cancer 9:149
Pan, Sheng; Cheng, Lihua; White, James T et al. (2009) Quantitative proteomics analysis integrated with microarray data reveals that extracellular matrix proteins, catenins, and p53 binding protein 1 are important for chemotherapy response in ovarian cancers. OMICS 13:345-54