To this end, the project team is developing small molecule modulators of glucocerebrosidase to help study cellular trafficking in these patients, and serve as starting points for therapeutics for Gaucher's disease, which is currently only treatable through enzyme replacement therapy. We are also developing physiologically relevant high throughput assays to study the effect of the compounds in preventing lysosomal storage of glucosyl ceramides and other lipids in the lysosomes of patient-derived cells. Gaucher disease results due to a lack of activity of the lysosomal hydrolase, glucocerebrosidase. During this period, the project team worked to design, optimize and miniaturize assays to monitor glucocerebrosidase, its functional activity, and accumulated lipids, in the lysosome of disease cells derived from patients. These assays will enable high-throughput screening of glucocerebrosidase to potentially discover and develop small molecule modulators of this important target.
| Mazzulli, Joseph R; Zunke, Friederike; Tsunemi, Taiji et al. (2016) Activation of ?-Glucocerebrosidase Reduces Pathological ?-Synuclein and Restores Lysosomal Function in Parkinson's Patient Midbrain Neurons. J Neurosci 36:7693-706 |
| Aflaki, Elma; Borger, Daniel K; Moaven, Nima et al. (2016) A New Glucocerebrosidase Chaperone Reduces ?-Synuclein and Glycolipid Levels in iPSC-Derived Dopaminergic Neurons from Patients with Gaucher Disease and Parkinsonism. J Neurosci 36:7441-52 |
| Zhu, Dongqing; Wu, Stephen; Carterette, Ben et al. (2014) Using large clinical corpora for query expansion in text-based cohort identification. J Biomed Inform 49:275-81 |
| Aflaki, Elma; Stubblefield, Barbara K; Maniwang, Emerson et al. (2014) Macrophage models of Gaucher disease for evaluating disease pathogenesis and candidate drugs. Sci Transl Med 6:240ra73 |
| Wieland, Mark L; Wu, Stephen T; Kaggal, Vinod C et al. (2013) Tracking health disparities through natural-language processing. Am J Public Health 103:448-9 |
