Lysosomal Storage Diseases
The Lysosomal Storage Diseases subtheme investigates target areas that are important for the pharmaceutical and biotechnology industries. Lysosomal storage diseases are inherited metabolic diseases, generally caused by the loss of function of a single enzyme. Unlike most human diseases, which have complex etiologies, the underlying defect in lysosomal storage diseases is generally well characterized.
Thus, they represent ideal systems for clinical investigation, as the molecular basis at the heart of the disease is known. Because they are caused by single genetic defects, lysosomal storage diseases have been the subject of intense clinical interest. Several therapeutic approaches are used in the clinic to treat lysosomal storage diseases, some approved by the FDA and others in clinical trials.
The lysosomal storage disease subgroup focuses on understanding the molecular basis of lysosomal storage diseases and on identifying potential new treatment avenues for these diseases. The Garman lab uses a variety of structural biology tools (including X-ray crystallography) to study lysosomal storage diseases. In addition to determining the structures of proteins used in enzyme replacement therapy clinical trials, the lab is also interested in small-molecule stabilization of lysosomal enzymes in pharmacological chaperoning (see figure).
The Kaltashov lab uses mass-spectrometry to monitor the stability of biologics, including those used in enzyme replacement therapy for lysosomal storage diseases.