COBRE for the Center for Molecular Medicine: Scope - Development of Specific Glucan Phosphatase Inhibitors

Glycogen and starch are critical energy storage macromolecules. Phosphorylation is the only known direct chemical modification of the glucose moieties in these macromolecules, and plays an important role in controlling their metabolism. This phosphorylation is controlled by glucan phosphatases. Glucan phosphatases not only have important physiological, but also pathological roles. We propose screening and structure/function studies focused on the development of specific inhibitors targeting human laforin and toxoplasma laforin. Emerging data indicates that human laforin has an important role in controlling cancer metabolism. Toxoplasma in an important human pathogen, which is difficult to treat due to its ability to enter into a quiescent chronic phase. We have recently demonstrated that toxoplasma laforin is critical for maintaining the chronic phase of infection, and so is an intriguing novel therapeutic candidate.