Decode molecular mechanisms of Parkinson’s disease

Poor handling and elimination of misfolded proteins has been identified as central in the molecular pathogenesis of Parkinson’s disease. A special class of proteins within the cell called “chaperones” is responsible for refolding misfolded or damaged proteins. If the chaperone system cannot adequately deal with these misfolded proteins, they are targeted to specialized disposal systems in the cell including the ubiquitin-proteasome system and the autophagy-lysosomal system. Together these pathways are critical to maintain protein quality control within a cell. If they are dysfunctional or overwhelmed, then neurodegeneration ensues. Our current work is aimed at dissecting these protein quality control mechanisms in Parkinson’s disease.

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Discover novel treatments for Parkinson’s disease

To discover disease-modifying therapies for Parkinson’s disease, we are understanding how dysfunction of molecular pathways cause neurodegeneration and developing novel tools and approaches for drug discovery. Our strategy is to use multiple experimental paradigms including traditional and innovative methods, as well as collaborative approaches with interdisciplinary teams. We are creating and deploying novel models of Parkinson’s disease, in combination with artificial intelligence, to define never before discovered molecular pathways that may contribute to neurodegeneration. These models allow us to test promising small molecules, as well as biological and cell therapies, to determine if they can halt the loss of dopamine neurons and be potentially translated to new therapies for Parkinson’s disease.

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Develop innovative applications of neuromodulation

Deep brain stimulation (DBS) has been established as a safe and effective way to modulate “circuitopathies” through mechanisms that remain largely unknown but likely include changes in gene expression in addition to regulating neuronal activity. Furthermore, DBS is a titratable and reversible therapeutic modality. We are currently testing the hypothesis that it is possible to combine DBS technology with gene therapy to create a novel and clinically useful method of spatio-temporal control of gene expression in the brain. Our strategy presents the intriguing possibility that DBS could be repurposed as a completely novel “electroceutical” therapeutic modality. This work is highly collaborative through CRANIA ( and involves scientists and clinicians at the Krembil Research Institute and KITE.