Cellular Compartmentalisation, Homeostasis and Inflammation
The delimitation and functional specialization of different compartments is a defining feature of our cells. Our view of these different organelles has changed remarkably during the last decade: far from being static, isolated spaces, the different cell compartments are extremely dynamic, engage in regulated intercommunication and contribute to coordinated adaptive responses of the cell to different conditionals. This coordination and integration of cell compartments with other cell functions and signalling networks holds keys to understand different complex aspects of disease. A prominent example is embodied by the endoplasmic reticulum (ER), which propagates imbalances in different functions it participates of (lipid metabolism, secreted protein maturation) to other cell systems such as signalling networks controlling cell growth and proliferation or apoptosis; these primarily adaptive mechanisms are essential contributors to several pathological conditions, including cardiovascular and neurodegenerative disorders, and cancer. However, we still have a limited understanding as to how the architecture and function of cell compartments are regulated, how this regulation feeds into and from other cell functions in healthy cells and tissues, and how their alteration influences pathological processes.
The long-term interest of our lab is to contribute to the better understanding of (1) how the architecture and function of specific cell compartments is regulated, and how their integrity is ensured; (2) how these regulatory mechanisms are integrated with signalling networks controlling inflammation and innate immunity, and cell adaption to the surrounding environment; and (3) how these principles modulate tissue repair and fibrosis, innate defence against pathogens, or aging-associated decline. The development of strategies for the combined use of omics technologies (proteomics, lipidomics, functional genetics) to achieve a systems-level understanding of these homeostatic processes and their dysfunction in disease is integral to our research.
Our current specific research lines explore the following topics:
1.- The crosstalk between the secretory apparatus (Golgi-ER interface) and innate immunity signalling.
2.- The role of ER function and its associated homeostatic signalling (UPR) in mechanotransduction and phenotypic transition control, with a particular focus on the response of endothelial cells to flow shear.
3.- Novel mechanisms of ER architecture remodelling in cell integrity and self-protection during defence responses.