I am a graduate student in the Koff lab here at Sloan-Kettering Institute. Our laboratory established that accumulation of p21 was necessary during growth factor induced gliomagenesis in mice, and identified a novel RING finger containing protein as a regulator of p21 ubiquitnation and accumulation. We and others have identified this protein as a tumor suppressor, and our data suggests that it suppresses growth through its ability to control p21. This suggests that a novel therapeutic strategy for glioma may rise from understanding the regulation of this protein and its ability to promote p21 ubiquitination.
My project focuses on the regulation of this E3 ligase and the identification of novel interacting proteins that may function upstream, downstream or with this E3 ligase to control p21 accumulation and growth suppression. I am using both biochemical and genetic screening approaches to identify new players in this pathway. In parallel, I am using biochemical and cell biological methods to determine whether post-translational modifications and/or changes in complexes regulate the relationship between p21 and its ligase. Ultimately, I hope to define part of this molecular pathway and thereby provide critical insight into the ability of p21 to act as an oncogene, and how it can be manipulated for therapeutic benefit.