The research interests of Wolfdieter Springer, Ph.D., revolve around cell biology in aging and age-dependent disorders. His primary research focus is on the molecular and cellular mechanisms underlying the pathogenesis of Parkinson's disease and other related neurodegenerative conditions.
Dr. Springer's Translational Cell Biology of Parkinson's Disease Lab combines biochemistry, cell biology and advanced imaging techniques, such as multicolor live cell and high-content microscopy. His lab aims to identify novel genetic and chemical modifiers through functional screening in cell-based and biochemical assays, and disease markers using multi-omics analyses. For validation, the lab employs CRISPR-Cas9 gene editing, patients' fibroblasts and induced pluripotent stem cell-derived cultures, as well as in vivo mouse models.
Dr. Springer is part of a team of internationally recognized researchers and clinicians with specialty training in Parkinson's disease and movement disorders supported by the American Parkinson Disease Association. Mayo Clinic has been designated an American Parkinson Disease Center for Advanced Research.
Selective mitochondrial autophagy. Dr. Springer and his team discovered a novel mitochondrial autophagy (mitophagy) pathway that links two Parkinson's disease-associated genes, PINK1, a mitochondrial ubiquitin kinase, and Parkin/PRKN, a cytosolic E3 ubiquitin ligase, as well as two of the main cellular dysfunctions implicated in disease pathogenesis.
The enzymes PINK1 and PRKN functionally interact to identify, label and target damaged mitochondria for selective degradation via autophagy. This emerging mitophagy pathway connecting mitochondrial processes to autophagic and lysosomal dysfunctions promises great potential for the development of beneficial therapeutics.
Mitochondrial and lysosomal dysfunctions. Intriguingly, mitochondrial as well as autophagic or lysosomal or both dysfunctions appear to play a major role in both the aging process itself and several neurological disorders.
Dr. Springer analyzes how disturbances in these organelles contribute to the aging process and the pathophysiology of several age-related human diseases, including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementias, lysosomal storage disorders and mitochondrial diseases.
- Biomarker discovery and structure-function-based drug design. Dr. Springer's research aims at a complete mechanistic dissection of the mitophagy pathway as well as the identification of novel key players, molecular disease signatures and auspicious drug targets. He and his colleagues are dedicated to translational biomarker and drug discovery efforts based on the understanding of the underlying disease mechanisms.
Significance to patient care
Functional insights gained through Dr. Springer's research will provide the basis to address unmet medical needs, such as identifying faithful biomarkers and developing novel therapeutic strategies that halt or prevent devastating neurodegenerative diseases.