MAPPING HEART FIBROSIS: INTEGRATIVE PHOSPHOPROTEOMIC PROFILING OF CLINICAL SAMPLES, ANIMAL AND ORGAN-ON-A-CHIP MODELS

Precision mass spectrometry, animal models and organ-on-a-chip (OOC) systems have emerged as promising experimental strategies to study the molecular mechanisms governing human biology and disease, including the molecular basis of cardiovascular disorders like fibrosis where access to patient samples is limiting and subject to confounding variables. Nevertheless, no systematic comparisons have ever been reported, precluding an objective assessment of cross-platform consistency, performance and bias. Here, we apply and evaluate an integrative mass spectrometry-based platform that allows for quantitative global phospho/proteomic surveys of normal and afflicted tissue from human, mouse and OOC-derived specimens. The applicability and utility of this approach was tested in the context of cardiac fibrosis through comprehensive analyses of fibrotic cardiomyocyte samples from Biowire OOC specimens, and cardiac tissue explants from hypertrophic patients and a mouse genetic model, and show that clinically meaningful biological inferences can be generated by leveraging commonalities and unique attributes generated across each platform.