Our laboratory is focused on basic mechanisms of regulated and aberrant gene expression during differentiation, tissue regeneration and cancer, especially as dictated by members of the p53- family, their interacting protein partners, and chromatin structure. We are using deep sequencing, proteomic analyses and bioinformatics to determine chromatin interactions, post-translational modifications and protein partners of p53. Our model systems of interest are embryonic stem cells, liver regeneration and breast cancer. A major focus is TRIM24, a previously unknown E3-ubiquitin ligase of p53 that we identified. TRIM24 co-activates estrogen receptor and is a histone reader of a unique signature present at estrogen-regulated genes in breast cancer cells. Additionally, we are currently defining the impact of TRIM24, and other p53 regulatory proteins, on p53-functions in embryonic stem cells, and how p53-mediated regulation is temporally controlled during liver regeneration.
Cascades of transcription regulation during liver regeneration