Our lab studies stress signaling pathways and the numerous factors that maintain proteins in a functional state in the human cell, often referred to as the proteostasis network. We aim to understand the function and dynamics of these networks in neurodegeneration and normal aging. We use a variety of techniques, ranging from biochemistry, cell biology, genetics, and genome-scale molecular approaches, to unravel the changes that take place in disease and to interrogate their function.
In the Walter lab at the University of California, San Francisco, I identified a potent small molecule that activates the translation initiation factor eIF2B and antagonizes the integrated stress response. Pharmacological modulation of this central pathway has many potential therapeutic avenues that we are exploring. In my graduate work, I studied the unfolded protein response and discovered that this signaling pathway is mediated by an unconventional cytosolic splicing event catalyzed by a unique kinase/RNAse IRE1 and tRNA ligase.