Structure-Function Analyses

Dr. Springer's Translational Cell Biology of Parkinson's Disease Lab has studied a series of missense mutations in PINK1 and PRKN (Parkin) that enable researchers to understand the molecular mechanisms of the pathway and its individual sequential steps, and to determine the pathogenicity of variants of unknown significance. The research team uses computational structural modeling to understand the specific molecular effects of genetic variants in PINK1 and Parkin and validate the findings in cell-based and biochemical assays. The team studies fibroblasts and directly converted (transdifferentiated) neuron cells under endogenous conditions.

Dr. Springer's team has discovered that certain heterozygous mutations can present risk factors for late-onset Parkinson's disease, further highlighting the importance of the pathway. This approach is also being used for a structure- and function-function based drug design and high-throughput screening of small molecules.

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