Meredith Irwin

Research Synopsis

Our lab is interested in pathways that regulate tumor cell death and chemosensitivity. We have two main areas of focus including:

• (1) p53 family protein signaling
• (2) novel signaling pathways and therapeutics aimed at neuroblastoma tumor initiating cells (TICs). P73 and p63 are two paralogues of the p53 tumor suppressor protein. We previously discovered that p73 is induced by chemotherapies and that the pro-apoptotic isoform (TAp73) mediates cell death in response to chemotherapies and other anti-cancer agents. Our studies have shown that p73 activity and stability is modulated by ubiquitination and neddylation and a current area of research involves elucidating the pathways that regulate these post-translational modifications of p73 and p63 in cancer and human disease. A second line of study involves the identification of novelp73 and p63 binding partners. We found that SATB2 (special AT-rich binding partner-2) binds to certain p63 and p73 isoforms regulating their ability to induce apoptosis in response to chemotherapy. Preliminary data demonstrates an exciting role forSATB2 in survival and metastases in certain solid tumors. We are also determining the role of other novel p73 and p63 interacting proteins identified in our screens.