Ph.D. 1995, University of Alabama, Birmingham
Phosphoinositide regulation of calpain in glioblastoma cell migration.
The lab's interest in the regulation of cell adhesion and migration by phosphoinositide 3-kinase and its lipid product PtdIns (3,4,5)-P3 have led us to investigate the invasion of tumor cells in the brain. Glioblastoma, which accounts for 20% of all primary brain tumors and is the most malignant form of brain cancer, is a devastating diagnosis with a 5-year survival rate of less than 4%. Although the mechanisms responsible for the carcinogenesis and progression of glioblastoma tumors are unknown, several gene mutations have been identified in glioblastoma cells. For example, protein mutations resulting in overproduction of the lipid PtdIns (3,4,5)-P3 have been identified to play a key role in the migration and invasion of glioblastoma cells. Our preliminary results suggest that PtdIns (3,4,5)-P3 is an important regulator of calpain proteolysis.
Calpain is a calcium-activated protease which cleaves several cytoskeletal adhesion proteins involved in cell motility and inhibition of calpain activity reduces tumor cell migration and invasion. The mechanisms regulating the proteolysis of proteins by calpain and the role of this posttranslational modification during migration are not clear. Understanding the function and regulation of calpain during the migration of tumor cells is expected to lead to the identification of new approaches for controlling cancer by targeting the activities of calpain.
One of the most exciting accomplishments this past year was the development of a zebrafish model to study tumor cell dispersal in the brain.