Biomarker and Drug Development
In addition to identifying novel genes that modify the pathway, Dr. Springer's Translational Cell Biology of Parkinson's Disease Lab aims to understand the molecular signals involved in its regulation. Combinations of phosphorylation and ubiquitylation govern selective autophagy pathways, such as mitophagy. Ubiquitin itself is phosphorylated and conjugated to mitochondrial substrate proteins by PINK1 and PRKN (Parkin), and the autophagy adaptor proteins that decode the specific ubiquitin signals also are modified themselves. The lab is investigating these novel, post-translational modifications in the disease context in clinical and pathological specimens.
Dr. Springer's research team is also exploring fundamental changes in the transcriptome, proteome and metabolome of PINK1 or Parkin mutant cells through an integrated approach to identify mitophagy-related disease signatures that can be applied to people with sporadic Parkinson's disease for improved stratification. At the same time, the lab is developing small molecules through structure- and function-based drug design and high-throughput screening of chemical libraries to identify and develop compounds that enhance clearance of damaged mitochondria and ameliorate dysregulated organelle homeostasis.
- Watzlawik JO, Hou X, Fricova D, Ramnarine C, Barodia SK, Gendron TF, Heckman MG, DeTure M, Siuda J, Wszolek ZK, Scherzer CR, Ross OA, Bu G, Dickson DW, Goldberg MS, Fiesel FC, Springer W. Sensitive ELISA-based detection method for the mitophagy marker p-S65-Ub in human cells, autopsy brain, and blood samples. Autophagy. 2021; doi:10.1080/15548627.2020.1834712.