NIH Funds Neglected Tropical Disease Research

The National Institutes of Health Exploratory/Developmental Research Grant Program (R21) funding mechanism is intended to encourage high risk but potentially high impact research. Prof. Karen Allen and her collaborator at the University of New Mexico, Prof. Deborah Dunaway-Mariano, have received a two-year R21 award to understand the structure and function of trehalose-6-phosphate phosphatase (T6PP), an enzyme identified in screens of C. elegans as a potential therapeutic target for infectious diseases caused by parasitic nematodes: lymphatic filariasis.
Lymphatic filariasis, commonly known as elephantiasis, is a mosquito-transmitted disease. Disfiguring and debilitating, it is endemic to 81 countries and affects 120 million people. A “neglected tropical disease,” there are currently very few medicines available to treat these infections and resistance to current approaches is emerging. This work will develop a greater understanding of T6PP structure and function, with an eye toward drug development. Profs. Allen and Dunaway-Mariano and their groups aim to capture multiple conformational states of the enzyme to develop a highly detailed analysis of the enzyme’s chemistry and possible regions to target by small molecule inhibitors. Furthermore, they will design and test inhibitors of the T6PP. The work is very likely to yield valuable information regarding the function and inhibition of an enzyme family that is currently under-examined as a therapeutic target.