Our lab is interested in determining how neurodegenerative diseases progress and cause toxicity to many different cell types throughout our bodies. Most neurodegenerative diseases are characterized by the abnormal misfolding of a particular protein, leading to the formation of protein aggregates inside or near neurons and glia in our brains. Our research aims to uncover the molecular mechanisms that regulate protein aggregate-related toxicity in cells. We primarily use the model genetic organism, Drosophila melanogaster (the fruit fly), for our studies because of its vast collection of genetic tools that enable us to manipulate gene expression in various cell types throughout the fly body. Using a fruit fly model of the inherited neurodegenerative disorder, Huntington's disease, we have previously established that pathogenic aggregates formed by mutant huntingtin spread between neurons and glial cells in a manner similar to infectious prions (Pearce et al, 2015, Nat Commun). The overarching goal of our current research is to identify conserved molecules and pathways that regulate prion-like aggregate spreading and aggregate-related toxicity in cells. This information will hopefully lead to the development of novel therapeutic strategies to treat millions of patients worldwide who suffer from neurodegenerative diseases.
Ongoing projects in the lab address the following questions:
1. How do pathogenic protein aggregates spread between neurons? What role do synapses play in this spread?
2. How do phagocytic glia prevent and/or contribute to aggregate-related pathogenesis in the brain?
3. What molecular pathways drive aggregate-related toxicity in cells?
4. How does protein aggregation affect different cell types in the body?