Cell death is involved in diseases such as cancer and neurodegeneration, and also has a natural role in the development of multicellular organisms. Although apoptosis has been well defined, alternative forms of cell death have been less explored. In my lab, we performed a global analysis of pharmacologically accessible cell death mechanisms using a strategy we refer to as modulatory profiling. Using this approach, we found compounds that induce apoptosis, necrosis, and a novel form of regulated cell death. These novel compounds induce a non-apoptotic, iron-dependent oxidative form of cell death that we refer to as ferroptosis. We have found that this form of cell death is distinct from apoptosis and necrosis on the basis of morphological, biochemical, genetic and inhibitor sensitivity data. In addition, we have used these compounds to elucidate the key mechanisms regulating ferroptosis, and to probe the relevance of ferroptosis to a variety of diseases and therapeutic applications. Finally, we have defined biomarkers that predict sensitivity and resistance to ferroptosis, opening the possibility of precision medicines that induce ferroptosis for treating a variety of cancers.
1. Design experiments to test the mechanism of cell death occurring in a specific context
2. Predict whether a specific patient will be sensitive to a drug that activates a specific type of cell death