The Lehrbach lab at Fred Hutch studies protein degradation, the process by which cells remove defective or unneeded proteins. When protein degradation fails, buildup of damaged or misfolded proteins causes cellular dysfunction and can lead to disease. High levels of abnormal or damaged proteins is a feature of aging, cancer, adult-onset neurodegenerative diseases, and many rare genetic conditions.
Our lab uses the microscopic worm, C. elegans, to uncover the fundamental processes by which cells dynamically control protein degradation; making discoveries that will help enable the development of new treatments for neurodegenerative diseases and cancer.
Protein Sequence Editing of SKN-1A/Nrf1 by Peptide:N-Glycanase Controls Proteasome Gene Expression
Lehrbach NJ, Breen PC, Ruvkun G. Cell. 2019.
Endoplasmic reticulum-associated SKN-1A/Nrf1 mediates a cytoplasmic unfolded protein response and promotes longevity
Lehrbach NJ, Ruvkun G. Elife. 2019.
Proteasome dysfunction triggers activation of SKN-1A/Nrf1 by the aspartic protease DDI-1
Lehrbach NJ, Ruvkun G. Elife. 2016.