Cell death is an inherent and essential aspect of life. This crucial cellular event is maintained by a finely tuned balance between cell survival and cell death which, when disrupted, has been linked to pathological conditions such as neurodegenerative disorders and carcinogenesis. Cell death modalities were broadly divided into programmed and accidental, which later came to be known as apoptosis and necrosis, respectively. This concept overlooked the emerging notion that necrotic forms of cell death are in fact regulated and kept in check by defined survival pathways.
Cell death pathway
Among these regulated necrotic cell death modalities considerable attention has been given to ferroptosis, a cell death pathway that requires phospholipid peroxidation. Our previous work has helped to characterize this pathway where we identified glutathione peroxidase 4 (Gpx4) as an essential regulator of this pathway. Moreover, we shed light into critical metabolic requirements linked to lipid metabolism that determines sensitivity to ferroptosis. Among our current interest are the discovery and characterization of novel nodes regulating ferroptosis and factors regulating them. In addition, we are pursuing the biochemical events linking phospholipid peroxidation and cell death with a particular interest in the role of lipid-derived electrophiles as potential second messengers. In order to track our goals we rely on a broad array of technologies and collaborations spanning from classical molecular biology and biochemistry, proteomics, CRISPR/Cas9 based screen and engineered cellular models and ultimately in vivo mouse models.
Our long term goal is to provide the rationale for novel pharmacological approaches that will enable us to tip the balance between life and death decision made by a cell, knowledge that will ultimately result in previously unforeseen therapeutic opportunities to treat disorders were unregulated cell death is a root cause.
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Supervisor – Biomedicine