Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder and is characterized by the irreversible loss of dopamine (DA) neurons in the substantia nigra pars compacta. Although the origin of DA neuron pathogenesis in PD remains elusive, corollary evidence suggests both genetic and environmental contributions. Our laboratory utilizes the genetic model Caenorhabditis elegans (C. elegans) to identify and characterize the molecular components involved in PD and environmental toxicant-induced DA neuron degeneration, and to screen for therapeutic targets and leads that may inhibit the pathology. Our prior studies established the first C. elegans toxicant and genetic PD models, and we are exploiting this system to identify and characterize the molecular determinants involved in DA neurodegeneration and the role that environmental compounds play in DA neuron vulnerability and neuropathology.
Our laboratory addresses the following fundamental questions:
- What are the molecular components involved in DA neuron vulnerability?
- What are the genetic and molecular pathways involved in manganese (Mn)- and methylmercury (MeHg)-induced DA neuron degeneration?
- How do PD-associated proteins contribute to DA neuron viability and cell death?
- What role do mitochondria play in DA neuron toxin vulnerability?
- Can we develop high-throughput in vivo chemical and genetic screens to identify endogenous molecules and xenobiotics involved in neurodegeneration and neuroprotection?