Discovery of Circulating Protein Biomarkers by Analysis of the Tissue Secretome

Learn how Caprion applies its label-free mass spectrometry-based proteomics platform to successfully identify tissue-specific protein biomarkers that can be used to follow disease progression in human blood.

Various aspects critical to a successful Discovery study will be discussed, including: (1) Identification of circulating biomarkers through the analysis of secreted proteins in the source tissue, (2) Determining tissue specificity through the creation of a secretome database in both human and rat, and (3) Statistical analysis of differential expression as well as building classifiers of disease and treatment outcome.

Though widely applicable to most diseases, drug targets and circulating fluids, a specific case study will be presented to illustrate the power and potential of the approach.

Case Study:

The progressive dysfunction of pancreatic ß-islets is central in diabetes pathogenesis. Proteins in the secretome of primary human ß-islets were identified under steady-state as well as in response to a challenge. Following the detection and quantification of over 2,000 proteins, approximately 300 were identified as candidates for detection in the circulation and of potential use as markers of ß-islet function. Assays were then established, either multiplexed MRM mass spectrometry or ELISA, to verify expression levels in plasma obtained from human subjects. A significant number of the candidate markers were found in plasma and were differentially expressed when comparing diabetic, pre-diabetic and healthy groups. Further, small panels of candidate biomarkers were able to effectively classify all clinical cohorts evaluated.

Speaker

Eustache Paramithiotis, Ph.D., Senior Director, Molecular and Cell Biology, Caprion

Eustache is responsible for all the experimental biology at Caprion. He leads the development of new biology applications for the CellCarta platform and has broad experience in target protein and biomarker discovery and validation in areas such as oncology, inflammation, and central nervous system disorders. He is the Principal Investigator of Caprion’s NIH/NIAID program in infectious disease.

Prior to the development of the CellCarta platform Eustache led Caprion’s mad cow disease diagnostic development program, resulting in the development of conformation-specific antibodies against aberrantly folded prion protein. He also has prior experience in homogeneous and heterogeneous assay development.

Eustache holds a B.Sc. in Biology from Concordia University and a Ph.D. in Immunology from McGill University. He did postdoctoral research in immune system development and memory at the Howard Hughes Medical Institute at the University of Alabama at Birmingham with an award from the prestigious Irvington Institute for Immunological Research.

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