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Proteomics Laboratory for The Environmental Determinants of Diabetes in the Young


EMSL Project ID
49637

Abstract

Type 1 diabetes mellitus (T1D) is a common autoimmune disease in children and results from autoimmune destruction of insulin-producing pancreatic ?-cells triggered by complex interactions of environmental factors and the immune system in genetically predisposed individuals. Although significant progress has been made in identification of both genetic risk and islet autoantibodies in disease prediction, the etiology of this disease remains unclear. High throughput technologies that provide comprehensive coverage of biomolecules can provide better understanding of the mechanisms behind developing islet autoimmunity and progression to T1D disease states. Proteomics approaches in particular can provide insight into the underlying pathways and protein networks involved, as well as identify peptides and proteins that may be utilized as predictive or diagnostic markers of developing disease.
The Environmental Determinants of Diabetes in the Young (TEDDY) is a consortium of investigators aiming to identify environmental factors that trigger the development of islet autoimmunity and T1D in genetically susceptible individuals. Children enrolled in TEDDY are at risk for T1D and have been prospectively followed with appropriate sampling at frequent intervals from birth up to the age of 9 (currently) and eventually up to the age of 15. This provides an ideal sample set for identifying signaling pathways or protein networks that are associated with developing disease and for testing the hypothesis that some of our previously reported peptide/protein markers might be linked with developing islet autoimmunity or with progression to T1D.
We propose to broadly identify and validate protein markers of developing autoimmunity as well as progression to T1D. In addition, we will provide basic proteomics support to the members of the TEDDY consortium by conducting GLP-like mass spectrometric analyses of peptide and protein abundances, and sharing these datasets with the TEDDY consortium through the TEDDY Data Coordinating Center. This will be achieved by leveraging our expertise in quantitative proteomics analyses, robust statistical analysis, and T1D biomarker discovery and validation.

Project Details

Start Date
2016-10-04
End Date
2019-09-30
Status
Closed

Team

Principal Investigator

Thomas Metz
Institution
Pacific Northwest National Laboratory

Team Members

Josue Cuevas Fernandez
Institution
Pacific Northwest National Laboratory

Ernesto Nakayasu
Institution
Pacific Northwest National Laboratory

Bobbie-Jo Webb-Robertson
Institution
Pacific Northwest National Laboratory

Richard Smith
Institution
Pacific Northwest National Laboratory

Related Publications

Stanfill B.A., E.S. Nakayasu, L.M. Bramer, A.M. Thompson, C.K. Ansong, T. Clauss, and M.A. Gritsenko, et al. 2018. "Quality Control Analysis in Real-time (QC-ART): A Tool for Real-time Quality Control Assessment of Mass Spectrometry-based Proteomics Data." Molecular and Cellular Proteomics 17, no. 9:1824-1836. PNNL-SA-129934. doi:10.1074/mcp.RA118.000648