Cancer cells can be highly dependent on specific nodes of the protein homeostasis network. This dependency can be exploited therapeutically. The defining example is multiple myeloma, a common blood cancer. Myeloma cells are hypersensitive to inhibition of the proteasome, which degrades cellular…
Genetic screens in mammalian cells provide important clues to the function of genes in normal and disease contexts. We have developed several complementary technology platforms to conduct such screens.
In collaboration with Peter Walter's lab at UCSF, we used our functional genomics approach to uncover the target of the drug-like molecule ISRIB. ISRIB was discovered in the Walter lab as an inhibitor of the integrated stress response, a central pathway in the mammalian proteostasis…
