Decoding the impact of microenvironment and signaling pathways in health and disease in brain, adrenal gland and kidney

Abstract

The Extracellular Matrix (ECM) differs greatly across organs owing to complex variations required for specific organ structure and function. ECM modulates cell behavior and regulates cell-cell interactions in physiological mechanisms, processes largely dependent on modulation of cell signaling pathways. Disruptions of these mechanisms may lead to disease. In the current project we propose to decode ECM composition, its interactions with different cellular components, and signaling pathways in homeostatic and pathological conditions of three organs that share individual cells with biological resemblance, namely brain, adrenal gland, and kidney. Our aims include: 1) to decode the ECM composition in health and disease by proteomic analysis; 2) to study the crosstalk between the ECM and the cellular components, concerning signaling pathways, by single-cell transcriptomic approach; 3) to address the impact of the ECM changes in experimental 2D, 3D and animal models; and 4) to identify novel therapeutic possibilities targeting ECM components and altered signaling pathways, by building a 3D organotypic model in a microfluidic platform for drug screening and generating strategic, novel omics data. We expect to identify (dis)similarities between human and experimental animal ECM composition to refine the validity of laboratory animal models to address human diseases. We also expect to determine key ECM components that impact on cellular phenotype and signaling pathways in health and disease. The use of 3D organotypic models including the unraveled ECM characteristics is expected to closely mimic human organs and reduce the number of animal experiments in pre-clinical trials. (AU)