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Author ORCID Identifier
Campus-Only Access for Five (5) Years
Doctor of Philosophy (PhD)
Molecular and Cellular Biology
Year Degree Awarded
Month Degree Awarded
Scott C. Garman
Daniel N. Hebert
Margaret M. Stratton
Eric R. Strieter
Biochemistry | Biophysics | Molecular Biology | Structural Biology
Lysosomal storage diseases affect about 1 in 5000 live births but most of them remain without treatment options. Fabry disease is commonly treated with enzyme replacement therapy, but kidney pathology remains problematic. We have engineered a smaller form of the treatment enzyme that should increase the concentration of protein that is able to reach a key part of the kidney filtration barrier, the podocytes. Our enzyme retains the ability to cleave Gb3, retains activity better than wild type in conditions relevant to enzyme replacement therapy and remains 99% identical to the wild type protein sequence. For another glycosidase deficiency, fucosidosis, we have established an expression system for the glycosylated form of alpha-L-fucosidase and demonstrate the potential of deoxyfuconojirimycin (DFJ) and fucose as pharmacological chaperones. Both chaperones were able to increase the lysosomal colocalization of the disease mutant S155F and both greatly stabilize the wild type enzyme at both acidic and neutral pH. These studies provide initial insights into two important treatment options for fucosidosis and warrant deeper investigations of both in cellular and animal models of the disease.
Butova, Cameron, "BIOCHEMICAL STUDIES OF FABRY DISEASE AND FUCOSIDOSIS" (2021). Doctoral Dissertations. 2281.
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