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
Internal Medicine/Medicine
Schools of Medicine
United States
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Nigjeh, Eslam N; Chen, Ru; Allen-Tamura, Yasuko et al. (2017) Spectral library-based glycopeptide analysis-detection of circulating galectin-3 binding protein in pancreatic cancer. Proteomics Clin Appl 11:
Chen, Ru; Lai, Lisa A; Sullivan, Yumi et al. (2017) Disrupting glutamine metabolic pathways to sensitize gemcitabine-resistant pancreatic cancer. Sci Rep 7:7950
Nigjeh, Eslam N; Chen, Ru; Brand, Randall E et al. (2017) Quantitative Proteomics Based on Optimized Data-Independent Acquisition in Plasma Analysis. J Proteome Res 16:665-676
Pan, Sheng; Brentnall, Teresa A; Chen, Ru (2015) Proteomics analysis of bodily fluids in pancreatic cancer. Proteomics 15:2705-15
Chen, Ru; Dawson, David W; Pan, Sheng et al. (2015) Proteins associated with pancreatic cancer survival in patients with resectable pancreatic ductal adenocarcinoma. Lab Invest 95:43-55
Pan, Sheng (2014) Quantitative glycoproteomics for N-glycoproteome profiling. Methods Mol Biol 1156:379-88
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
Shin, Soo J; Smith, Jeffrey A; Rezniczek, G√ľnther A et al. (2013) Unexpected gain of function for the scaffolding protein plectin due to mislocalization in pancreatic cancer. Proc Natl Acad Sci U S A 110:19414-9
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
Chen, Ru; Pan, Sheng; Ottenhof, Niki A et al. (2012) Stromal galectin-1 expression is associated with long-term survival in resectable pancreatic ductal adenocarcinoma. Cancer Biol Ther 13:899-907

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