Phosphoinositide kinases: Molecular determinants for their regulation and role in human disease

Lipids are the primary constituent of all cellular membranes, however, they also can play key roles as signaling molecules that controls how a cell responds to its environment.  Almost every aspect of a cell's decision to live and die is impacted by the role of lipid signals called phosphoinositides. These signals are generated in the correct location and at the appropriate time by proteins in our body called phosphoinositide kinases (PI kinases). Misregulation of PI kinases is a key driver of disease, including cancer and immunodeficiencies.

Intriguingly host PI kinases are frequently hijacked by pathogenic viruses to mediate viral replication, and targeted inhibition of parasite PI kinases is a promising therapeutic strategy for treatment of malaria and cryptosporidiosis (a diarrheal disease caused by microscopic parasites). Therefore, understanding the molecular basis for how PI kinases are regulated is of extreme biomedical importance.

Dr. Burke's research is focused on understanding the molecular basis for regulation of PI kinases, and how they are involved in human disease. He and his team have revealed fundamental insight into how these enzymes are involved in cancer and immunodeficiences, and how viruses manipulate them to mediate infection. Overall this work is important in understanding how lipid signals mediate disease, and will be critical in the design of inhibitors as novel therapeutics.