HNSCC (head and neck squamous cell carcinoma) is the sixth most common cancer worldwide and despite aggressive chemotherapy, surgery and radiation, survival is less than 50%. A protein called DNp63a (DeltaNp63alpha) is present in very high levels in HNSCC and can protect the cells from chemotherapy, preventing cell death. Therefore, understanding mechanisms that regulate DNp63a may provide insight into how HNSCC becomes resistant to chemotherapy. We have identified a protein called SATB2 that binds to DNp63a and our preliminary data suggests that it can regulate DNp63a function. In this research project, we will investigate the role of SATB2 in protecting HNSCC cells from chemotherapies commonly used as treatment (cisplatin, 5FU, doctaxel and radiation). We will also determine how SATB2 can regulate DNp63 to make cells more sensitive to chemotherapy drugs. A better understanding of pathways that govern HNSCC survival in response to chemotherapy will help us to identify new targets to develop more effective therapies.