Blood plasma/serum has remained a major sample source for the detection of disease biomarker candidates with its easy accessibility and measurable tissue-derived proteins that hold potential to uncover physiological and pathological changes during diseases. Proteomics-based biomarker discovery using plasma/serum, however, is severely limited by the high complexity and dynamic range of protein concentrations (10-12 orders of magnitude). Presently, a majority of plasma/serum proteomic strategies are lack of adequate reproducibility, sensitivity, and robustness for clinical tests. Solutions for these serious technological barriers to develop a reliable detection platform toward clinical implementation are elusive. The long term goal of this project is to establish a robust proteomic platform that is translational, sensitive, and reproducible for biomarker discovery, verification and validation, with an emphasis on the identification and validation of plasma biomarkers for metabolic syndrome and early detection of coronary artery disease (CAD). We propose to develop a distinctive platform based on metal ion functionalized soluble nanopolymers for efficient and selective isolation of subsets of low abundant plasma proteins. We will test this approach by focusing on Ossabaw swine as our model system and will establish protocols that will ultimately provide a powerful method for any biofluid-based biomarker discovery. We propose to profile plasma proteomes as a function of feeding time and to correlate with physiological and pathological parameters over the period in which the Ossabaw swine develop metabolic syndrome. There is an increasingly urgent and strong push of proteomic discoveries to clinical applications. This project is based on a distinctive new concept and once developed, it will dramatically simplify the procedure and enhance our ability to sensitively identify candidate markers. As a consequence, the results of this study will have an important positive impact, not only on the development of novel tools for proteomics-based biomarker discovery, but also toward improving disease therapeutics and facilitating more effective diagnosis.

Public Health Relevance

Early detection of coronary artery disease (CAD) can save numerous people?s life by providing earlier and better disease diagnosis, improved prognosis for patient monitoring, and preventative screening that can identify patients at highest risk. This NIH RO1 application will develop a novel platform for biomarker discovery which will couple with a large animal model for accurate and efficient identification of protein markers for metabolic syndrome and onset of CAD.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM111788-01A1
Application #
8887497
Study Section
Enabling Bioanalytical and Imaging Technologies Study Section (EBIT)
Program Officer
Edmonds, Charles G
Project Start
2015-09-15
Project End
2018-08-31
Budget Start
2015-09-15
Budget End
2016-08-31
Support Year
1
Fiscal Year
2015
Total Cost
$297,113
Indirect Cost
$99,613
Name
Purdue University
Department
Biochemistry
Type
Schools of Earth Sciences/Natur
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907
Li, Liyuan; Qian, Maoxiang; Chen, I-Hsuan et al. (2018) Acquisition of Cholangiocarcinoma Traits during Advanced Hepatocellular Carcinoma Development in Mice. Am J Pathol 188:656-671
Wang, Pengcheng; Zhao, Yang; Li, Zhongpeng et al. (2018) Reciprocal Regulation of the TOR Kinase and ABA Receptor Balances Plant Growth and Stress Response. Mol Cell 69:100-112.e6
Arrington, Justine V; Hsu, Chuan-Chih; Elder, Sarah G et al. (2017) Recent advances in phosphoproteomics and application to neurological diseases. Analyst 142:4373-4387
Hsu, Chuan-Chih; Xue, Liang; Arrington, Justine V et al. (2017) Estimating the Efficiency of Phosphopeptide Identification by Tandem Mass Spectrometry. J Am Soc Mass Spectrom 28:1127-1135
Zeng, Lingfei; Wang, Wen-Horng; Arrington, Justine et al. (2017) Identification of Upstream Kinases by Fluorescence Complementation Mass Spectrometry. ACS Cent Sci 3:1078-1085
Chen, I-Hsuan; Xue, Liang; Hsu, Chuan-Chih et al. (2017) Phosphoproteins in extracellular vesicles as candidate markers for breast cancer. Proc Natl Acad Sci U S A 114:3175-3180
Pan, Li; Aguilar, Hillary Andaluz; Wang, Linna et al. (2016) Three-Dimensionally Functionalized Reverse Phase Glycoprotein Array for Cancer Biomarker Discovery and Validation. J Am Chem Soc 138:15311-15314
Iliuk, Anton; Galan, Jacob; Tao, W Andy (2009) Playing tag with quantitative proteomics. Anal Bioanal Chem 393:503-13