Our research aims to understand how intracellular contact sites control cell fate and to translate this knowledge into new opportunities to counteract neurodegeneration. We study the molecular mechanisms that shape the architecture, function and plasticity of interorganellar contact sites, how these structures adjust to the demands of aging and stress, and how their malfunction contributes to disorders such as neurodegeneration and cancer. Our work also includes drug-discovery efforts to identify molecules that can correct early intracellular defects and help restore the cellular balance that is lost in disease.

A major focus of the lab is the study of mitochondria–endoplasmic reticulum contact sites (MERCS), key hubs coordinating mitochondrial dynamics, metabolism, calcium handling, stress adaptation and regulated cell death. Because MERCS are highly dynamic and heterogeneous, their analysis has long been technically challenging. To overcome this, we develop and apply advanced tools that allow us to monitor, characterize and manipulate these structures in physiologically relevant conditions and across diverse cellular systems.

Among the molecular players we investigate, BCL-2 family proteins are of particular interest—not only as master regulators of apoptosis, but also due to their essential “day-job” roles in shaping MERCS-mediated processes such as mitochondrial dynamics, metabolic control and stress signalling, all of which become disrupted in disease. By integrating these perspectives, we explore how MERCS–BCL-2 crosstalk modulates cellular resilience and contributes to early vulnerability in neurodegenerative disorders.

Our toolkit includes MERLIN, a custom BRET-based biosensor that quantifies mitochondria–ER distance in living cells without perturbing their native organization, proximity-dependent biotinylation coupled to mass spectrometry for MERCS proteomics, and imaging approaches ranging from confocal and STED microscopy to electron microscopy. Together, these technologies enable us to dissect the earliest MERCS alterations that precede mitochondrial dysfunction and contribute to the intracellular vulnerabilities that drive disease.