FEB 24, 2016 11:00 AM PST

Precision Ferroptosis Inducers: Death by Lipid Peroxidation

Speaker
  • Professor, Columbia University, Departments of Biological Sciences and Chemistry
    Biography
      A decorated researcher, Stockwell is investigating mechanisms of cell death and exploring their application in the treatment of cancer and neurodegeneration. His investigations have not only identified drug candidates, they've inspired new methods of small molecule drug discovery. Stockwell is author of The Quest for the Cure: The Science and Stories Behind the Next Generation of Medicines.

    Abstract

    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.

    Learning Objectives:
     
    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

     


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