Our laboratory studies molecular mechanisms that promote head and neck cancer development, with a primary focus on squamous cell carcinoma (SCC) and salivary adenoid cystic carcinoma (ACC). Head and neck cancer results from the accumulation of genetic alterations, which may lead to the disruption of signaling pathways that control cellular functions, including proliferation, cell death and differentiation. We are interested in understanding how some of the most prevalent genetic alterations found in patients with these malignancies contribute to tumor development, using mouse models as the primary experimental system. More specifically, we are studying the function of p53 mutations in SCCs, with an emphasis in dissecting the role of loss-of-function and gain-of-function mutations in the p53 gene, during SCC development and in response to therapy. We are also interested in studying the cooperation between mutations in the p53 and Cdkn2a genes during SCC progression and metastasis. In addition, we are generating new transgenic mouse models for ACC, based on the expression of Myb alterations, which are found in most of the human ACCs. These models are expected to enhance our understanding of the biology of this disease and to be useful tools to identify targeting strategies for Myb, particularly in light of the lack of experimental systems for ACC, including human cell lines. Analysis of genes and pathways altered in Myb-induced tumors and cross-species analysis with human ACCs are expected to identify key mechanisms involved in ACC development and tumor maintenance.