The Unfolded Protein Response and IRE1 Signaling in Health and Disease
The unfolded protein response maintains protein homeostasis in the endoplasmic reticulum (ER), where the majority of transmembrane and secretory proteins are modified, folded and assembled. When the ER-resident folding machinery becomes overwhelmed, misfolded polypeptides accumulate and lead to ER stress, with toxic consequences to cells. Read more…
Organellar quality control, dynamics, and inheritance
Organelles are subcellular compartments that provide optimized conditions for distinct biochemical reactions. Due to their utmost importance for the cell’s survival, organelle inheritance and integrity is faithfully and continuously monitored. Read more…
RNA processing in the Unfolded Protein Response
Ire1-mediated signaling during the unfolded protein response encompasses fascinating aspects of basic RNA biology including mRNA targeting, cleavage, and turnover as well as mRNA quality control. Read more…
The integrated stress response and its role in cognition
Cells maintain their proteins in a functional and balanced state by regulating protein synthesis, folding, trafficking and degradation. A central regulatory target in this process is the nucleotide exchange factor eIF2B, which we can now regulate using the recently discovered small molecule ISRIB. Read more…
ATF6-branch signaling through regulated proteolysis
One family of proteins that senses conditions in the ER and increases the organelle’s folding capacity is comprised of a family of membrane-bound transcription factors, named after the founding member ATF6. We are interested in the molecular mechanisms behind the activity of ATF6 family proteins, as well as their functional roles in the cell. Read more…