Functional characterization of proteins involved in organelle-associated metabolic disorders and syndromes

 

The lysosome is the primary site for the intracellular degradation of metabolic. Defects in genes that encode lysosomal or lysosomal-associated proteins can result in the abnormal build-up and subsequent storage of metabolic wastes. These defects lead to lysosomal storage diseases (LSDs), which include over 70 genetically distinct metabolic disorders. Despite the fact that the causative genes are known and most mutations have been reported, the molecular and cellular mechanisms underlying each distinct LSD remain obscure. To elucidate these mechanisms, our lab utilizes subcellular immunopurification tools and harnesses the power of multi-omics approaches such as metabolomics, proteomics, and functional genomics. Indeed, our recent discovery has been facilitated by using lysosomal immunopurification (LysoIP) from cultured cells (LysoTag cells) and animal models (LysoTag mouse) of CLN3-Batten disease in combination with untargeted metabolomics and lipidomics analyses (Laqtom, NN. et al., 2022) In addition to LSDs, our lab is interested in studying: 1) the function of the endosomal protein TBC1D24, the deficiency of which results in DOORS syndrome, and 2) the function of the ER-resident CYBC1 protein, the loss of which causes an immunodeficiency disorder of phagocytes (CGD).