Cell compartments and signaling
The overall objective of our team is to understand how the signals originated in the cell surface are transduced to trigger reactions that lead metabolic changes, proliferation, or survival and how these mechanisms are affected during disease. The research is organized at three levels: i) Endocytosis and exocytosis of proteins, ii) intracellular transport and storage of lipids, and iii) signal transduction pathways and cell cycle. In this complex scenario we are currently studying the endocytic compartment, lipid droplets, the transport between the nuclei and the cytosol, the endoplasmic reticulum, the microdomains existing on the plasma membrane, and the signalling pathways that regulate the cell cycle and apoptosis.
Main lines of research
Endocytosis and intracellular trafficking of proteins and cholesterol: The general objective is the study of the mechanisms that regulate the endocytosis and exocytosis of proteins and cholesterol and the signalling pathways associated with these processes. Our main projects focus on determining the role of Annexin A6 (AnxA6) in the regulation of these pathways:
- Annexin A6 and Signalling.
- Annexin A6 in Membrane Trafficking and Organization.
- Role of Annexin A6 during Liver Regeneration.
Lipid trafficking and disease: The aim of our project is to characterize the cellular mechanisms that regulate the transport and storage of lipids. Our research has four main subjects: lipid droplets, mitochondria, caveolin, and cholesterol. Our lines are:
- Mechanisms of Lipid Droplet Biogenesis, Accumulation and Metabolism.
- Caveolin and the intracellular trafficking of cholesterol, implications on cell metabolism, proliferation and apoptosis.
- Hepatic and Brain Mitochondrial Cholesterol in Health and Disease.
Signal transduction and cell cycle: The overall objective of the group is to analyse the signal transduction mechanisms that regulate cell cycle progression and their alterations in oncogenesis. Specifically we are studying the function and regulation of the Ras and Rho family of GTPases in different intracellular compartments/platforms, and the signal transduction pathways involved in the response to replication stress. Our research lines are:
- Regulation of K- Ras, Rac1 and Cdc42 function by binding to calmodulin and by phosphorylation.
- Study of the endocytic compartment as a signalling platform.
- DNA Replication and DNA damage stress responses in normal and tumour cells.
Endocytosis and intracellular trafficking of proteins and cholesterol
Our group is interested on the molecular mechanisms of membrane traffic in mammalian cells. This basic research is important for understanding a number of diseases including cancer, diabetes, and heart disease or liver disorders. We study the regulation of a variety of aspects of protein and cholesterol trafficking and signal transduction in the endocytic compartment; a sorting and processing station for proteins internalized by cells as well as of the secretory pathway. We are focus in the study of Annexin A6. Annexins are an evolutionarily conserved multigene family with roles in vesicle trafficking, phospholipid metabolism, actin dynamics, apoptosis and cell transformation.
Signal transduction and cell cycle
Our group is interested in studying signal transduction pathways activated upon proliferative signals or upon replication stress and their alteration in tumorigenesis. Specifically we analyse the regulation of GTPases proteins of the Rho and Ras family signalling from different plasma membrane and endocytic platforms, and implications of this signalling compartmentalization in various cellular processes such as proliferation, cell migration and mobility, and also in oncogenesis. We are also analysing signalling from arrested replication forks that lead to cell cycle arrest and senescence.
Trafficking and disease
Lipid droplets are organelles that collect, store and supply lipids in all eukaryotic cells. However, these organelles are also cellular hallmarks of prevalent diseases ranging from obesity to cancer. The cell biology of lipid droplets and its role in pathogenesis are still unclear. Our group is interested in the mechanisms of lipid droplet biogenesis and consumption.
A cholesterol imbalance in cells –by high ingestion or trafficking defects - has important cellular and physiological consequences. Cholesterol accumulation promotes mitochondrial dysfunction and oxidative damage underlying in the pathogenesis of steatohepatitis, neurodegeneration and atherosclerosis. In this context, we are especially interested in how caveolin-1 regulates cholesterol trafficking and storage.