Grant: Operating Grant

ALK and LTK are two highly related proteins that are most highly expressed in the brain. It has been known for several years that aberrations in ALK that lead to inappropriate expression and increased protein activity are associated with various neuronal and other cancers. Indeed, clinical trials with ALK inhibitors are currently underway. It is thus remarkable that virtually nothing is known of the normal role of these proteins. We have recently shown that these proteins play a role in controlling the formation of the shape of normal neurons, a fundamental process that is also modified during cancer progression. Here we propose to use mouse models as well as biochemical, molecular and cell biological approaches to determine the normal function of these proteins. We expect that understanding how these proteins normally work in the brain will help us develop methods to treat neurological disorders and will assist in the development of more potent or specific inhibitors for use as therapeutics for brain-derived and other cancers.