We are interested in how the acid-base chemistry of the tumor microenvironment affects cancer cell biology, and how this interaction may influence the disease trajectory.  The central aim of the project is to describe how different PDAC cancer cell lines respond to various levels of acidity, using readouts that include proliferation, differentiation and invasion with high-throughput methods.  The genetic or epigenetic basis for an acid-resistant or acid-sensitive phenotype will be identified by sequencing, and then tested experimentally by genetic manipulations.  Finally, the relevance of these findings to tumor growth and metastasis will be tested in mouse xenograft models.  A parallel aim is to use computational models to describe the findings systematically, and curate databases that can link hitherto unexplored phenotypic variables with genetic information.