Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Cells of the immune system must circulate the body to survey and respond to infection. Much the way whole organisms achieve locomotion, individual immune cells coordinate external stimuli to intracellular structure built through cytoskeletons. In order to change shape and get through tissues and vasculature, immune cells must remodel their cytoskeletons by breaking them down into units which can be used in rebuilding. Because these cells are highly migratory, should they lose control over growth mechanisms, they can develop into particularly aggressive cancers called lymphomas. Though strategies to combat lymphoma have greatly improved in the past thirty years, more than 20,000 deaths each year result from the disease, often affecting younger populations. Therefore, finding new therapies and drug targets is a highly beneficial pursuit in this field. In many other cancer types, the activities of molecules which drive cytoskeletal remodeling are enhanced; however, this is less well understood in lymphomas. We study one of these molecules called the Rap GTPase which connects cytoskeletal remodeling to external stimuli. We have recently found that one mode by which Rap does this is through an actin binding protein, cofilin. Cofilin is one of those molecules which help breakdown the cytoskeleton into units which can be reused in rebuilding. In other cancer types, both Rap and cofilin activities are enhanced which increases the ability of these cells to remodel their cytoskeleton, migrate, and spread to distant organs of the body, a process called metastasis. We are now investigating if these activities are also enhanced in lymphoma and if this signaling is needed for lymphoma cells to spread throughout the body. Should Rap and cofilin activities be increased in aggressive lymphomas and collectively make lymphoma cells better at spreading to distant organs, this may be a novel pathway to target with drugs in the hope to make these cancers less harmful.