Research at the Gu Lab

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The Gu Lab focuses on elucidating how cells regulate proteasomal degradation independently of ubiquitination. We discovered a non-canonical proteolysis mechanism, the midnolin-proteasome pathway, that bypasses ubiquitination to selectively degrade numerous stimulus-responsive and cell-type specific transcription factors including EGR1, IRF4, Fos, NeuroD1, STAT3, and NR4A1. The Gu lab will characterize the midnolin-proteasome pathway using biochemical, structural, and cellular experiments. Additionally, genetically engineered animal models will be used to determine the roles of midnolin in organismal physiology and pathology. The long-term goal is to manipulate the midnolin-proteasome pathway either genetically or pharmacologically to control brain functions, modulate the immune system, and destroy cancer cells.

​The Gu lab is also interested in identifying other ubiquitin-independent mechanisms that degrade different substrate repertoires as well as the crosstalk of protein homeostasis with chromatin biology and metabolism. Overall, we seek to elucidate fundamental mechanisms related to cell biology using a diverse experimental tool kit.