Prof. Dr. Ana J. Garcia Saez

Research Priorities: Molecular mechanisms of regulated cell death, membrane organisation, permeability and dynamics, mitochondrial changes, apoptosis, cancer
Ana J. García-Sáez is a Spanish biochemist and chemist. She is researching regulated cell death and its underlying physical principles and molecular mechanisms. She has used state-of-the-art microscopic methods to visualise individual cells or molecules to give essential insights into the organisation and dynamics of membranes as well as mitochondrial changes during apoptosis. Understanding the principles of regulated cell death and its failure in the case of certain diseases, such as cancer, opens up new possibilities for therapy.
Regulated cell death, or apoptosis, is a natural process in which the organism eliminates damaged cells. Ana J. García-Sáez has become known for researching the underlying processes. Together with her team, she is investigating how membrane behaviour and signalling are coordinated by the interaction of several molecular components and the mechanical properties of the membrane. She is particularly interested in mitochondrial changes and membrane permeabilisation as common features of regulated cell death.
Ana J. García-Sáez’s team shaped our understanding that pore formation in the outer mitochondrial membrane is a pivotal step in apoptosis. It leads to the release of apoptotic factors such as cytochrome c into the cytosol, which activates certain protein-cleaving enzymes, caspases, and thus triggers cell death. Ana J. García-Sáez uses biosensors that she developed herself and special microscopic methods to investigate the full network of proteins involved in the interaction. She has shaped our understanding that some proteins (such as BCL-2) inhibit apoptosis, while others (such as BAX or BAK) mediate the permeability of the outer mitochondrial membrane and BH3 proteins act as sensors for the various apoptotic stimuli and initiate apoptosis.
Since BCL-2 proteins play an important role in tumour development and in cellular responses to cancer therapies, understanding how they work is of enormous therapeutic interest. The research group of Ana J. García-Sáez is investigating the stoichiometry and interaction preferences of BCL-2 protein complexes using state-of-the-art microscopic methods that enable them to visualise individual cells and individual molecules in the cell.
They are also investigating the composition, dynamics, and structure of apoptotic oligomers. The objective is to understand how these are integrated in order to orchestrate the function. The mechanisms underlying mitochondrial dynamics and the contacts of mitochondria with other cell membranes are also a focus of her work.
Understanding the mechanisms that lie behind regulated cell death may contribute to developing or improving medical therapies.