KBTBD4 Cancer Hotspot Mutations Drive Neomorphic Degradation of HDAC1/2 Corepressor Complexes

Olivia Zhang recently obtained her Ph.D. in Chemistry and Chemical Biology from Harvard University in Dr. Brian Liau’s Lab. Her research focused on understanding chemical and genetic mechanisms to regulate the LSD1-HDAC1/2-CoREST (LHC) repressor complex. In particular, she investigated the mechanism of cancer hotspot mutations in the E3 ligase KBTBD4 in promoting the degradation of CoREST. Using deep mutational scanning and a diverse array of biochemical and cell based assays, her work along with extensive collaborations reveal the mutational landscape of the KBTBD4 hotspot that can promote neomorphic protein-protein interactions that drive subsequent protein degradation. Her work aims to address how we can use genetic methods to uncover protein-protein interactions that can inform therapeutic applications