David J. Vocadlo

May 14, 2024 | nature.com | Emma Carroll |Carrie L. Partch |David J. Vocadlo

AbstractDifferential scanning fluorimetry (DSF) is a technique that reports protein thermal stability via the selective recognition of unfolded states by fluorogenic dyes. However, DSF applications remain limited by protein incompatibilities with existing DSF dyes. Here we overcome this obstacle with the development of a protein-adaptive DSF platform (paDSF) that combines a dye library ‘Aurora’ with a streamlined procedure to identify protein–dye pairs on demand.

Apr 28, 2024 | biorxiv.org | Adriano Aguzzi |Jiang-An Yin |David J. Vocadlo |Kathi Ging

AbstractMutations in the GBA gene, which encodes the lysosomal enzyme β-glucocerebrosidase (GCase), are the most prevalent genetic susceptibility factor for Parkinson's disease (PD). However, only approximately 20% of carriers develop the disease, suggesting the presence of genetic modifiers influencing the risk of developing PD in the presence of GBA mutations.

Oct 30, 2023 | jbc.org | Byrne M.D |Matthew R. Pratt |David J. Vocadlo |Simon FRASER

AbstractO-GlcNAc is a common modification found on nuclear and cytoplasmic proteins. Determining the catalytic mechanism of the enzyme O-GlcNAcase (OGA), which removes O-GlcNAc from proteins, enabled the creation of potent and selective inhibitors of this regulatory enzyme. Such inhibitors have served as important tools in helping to uncover the cellular and organismal physiological roles of this modification.

Apr 12, 2023 | nature.com | Vinod Udayar |Martino L. Morella |Verdon Taylor |David J. Vocadlo |Alexandra Gehrlein |Martin Ebeling

AbstractMutations in glucocerebrosidase cause the lysosomal storage disorder Gaucher’s disease and are the most common risk factor for Parkinson’s disease. Therapies to restore the enzyme’s function in the brain hold great promise for treating the neurological implications. Thus, we developed blood-brain barrier penetrant therapeutic molecules by fusing transferrin receptor-binding moieties to β-glucocerebrosidase (referred to as GCase-BS).

Feb 15, 2023 | mdpi.com | Edwin Escobar |Jesús E. Serrano-Negrón |David J. Vocadlo |Erin H. Seeley

Abstract: Simple SummaryPost-translational O-glycosylation of proteins with N-acetylglucosamine serves as a cellular regulator that has been linked to cancer. This sugar’s variability is emerging as a metabolic biomarker in cancer, and here we investigate the use of mass spectrometry imaging to visualize the location of this sugar in primary tumor sections.