Surenna Pecchia - 2025

     My research focuses on understanding how Wnt signaling is regulated by the 𝛽-catenin destruction complex and the centrosome in cells. The Wnt pathway converges at the 𝛽-catenin destruction complex (DC), a liquid-like structure that regulates cellular 𝛽-catenin levels and consequently, cell fate decisions. Truncatations in the DC scaffolding protein APC are highly prevalent in colorectal carcinomas. Previously, our lab identified that the centrosome, a key cell cycle regulatory hub, nucleates DC formation into liquid-like biomolecular condensates. 

     I utilized biotin proximity labeling (BioID) to interrogate molecular coupling of the DC and centrosome, as well as how Wnt pathway activation and cancer-causing mutations may alter this structure. After fusing DC scaffolds Axin and APC to BirA*, a promiscuous biotin ligase, I verified a tight biotin labeling radius around BirA* fusion proteins without perturbation of DC structure or localization. Streptavidin pull-down coupled with liquid chromatography mass spectrometry allowed me to identify several centrosomal and cell cycle regulatory proteins. Presently, I am working on validating highly enriched hits identified in mass spec by CRISPR knock-downs and CRISPR tagging. These experiments will help me further understand the role of DC-interacting proteins in regulating DC structure and/or cellular 𝛽-catenin levels.