Jieya Shao, PhD
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Washington University in St. Louis (WU)
We are interested in delineating the biology of novel anticancer targets. Our current focus is on two proteins – the actin-binding factor profilin-1 and the polyubiquitin-specific protein segregase p97/VCP. Profilin-1 is an essential gene for eukaryotic cells, yet showing paradoxical anti-cancer activities in multiple types of human cancer. We hypothesize that it has ‘moonlighting” nuclear functions which represses the expression of various pro-cancer genes, spatially separate from its actin-regulatory activities in the cytoplasm. This “spatial confinement” model reconciles its paradoxical cellular functions and is the main focus of our research effort. In parallel, we are studying p97/VCP which is an evolutionarily conserved AAA+ ATPase regulating cellular proteostasis via facilitating the turnover of a myriad of polyubiquinated proteins within various cellular structures and protein complexes. Our current interest is its role in chromatin-associated protein degradation which occurs dynamically during DNA damage response and is crucial for maintaining genome stability.