Many cancers arise as a result of the acquisition of a series of fixed DNA sequence abnormalities, termed mutations, which ultimately confer a growth advantage upon the cells in which they have occurred. These mutations can have several impacts on the gene in or near which they reside. Mutations that contribute to disease initiation or progression, often by altering the protein product directly, are termed “driver” mutations, whereas those mutations that are a result of the inherent genetic instability of the cancer, confer no selective advantage to the cell and do not contribute to disease progression are termed “passenger” mutations.  With the advent of Next Generation Sequencing (NGS) the identification of mutations in the genomes of healthy and diseased tissues has become commonplace providing a new avenue to discover potential genotypes underlying the molecular causes of cancers.

Our research focuses on using protein evolution and structural data to develop methods to assess the functional impact of mutations.