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Unravel the mechanisms of synaptic and axonal degeneration in Parkinson’s disease and aging, and translate these insights to promote brain health across the lifespan!
Why?
Upright walking, unique to humans, freed our hands and fueled our cognition, but also brought about distinctive movement disorders like Parkinson’s disease.
Now the world’s fastest-growing neurological disorder, Parkinson’s affects over 10 million people globally, primarily among the aging population, with about 1 million in the U.S.
In light of its significant impact, the U.S. government has initiated a National Plan to End Parkinson’s, a goal that hinges on our understanding of the disease’s underlying mechanisms.
What?
Neurodegenerative processes in Parkinson’s disease arise from an interplay between aging and genetic/environmental factors. The primary sites of degeneration are dopamine-producing neurons in the nigrostriatal network of brain.
While it is established that synapses of these neurons degenerate before the cell bodies, the mechanisms behind this synaptic degeneration and its role in the overall disease process remain unclear.
Our lab aims to address this gap by studying novel Parkinson’s-related mutations in presynaptic endolysosomal proteins, examining how these mutations interact with genetic and environmental risk factors, as well as aging.
How?
Our team is pursuing this goal through three comprehensive studies that integrate mechanistic investigations using mouse models, patient-derived and CRISPRed iPSC neurons, SH-SY5Y cell lines, and patient biospecimens.
We will employ a diverse range of advanced techniques in histopathology, microscopy, biochemistry, subcellular proteomics, mouse behavior, viral gene manipulations, and various cell biology methods.
Additionally, we will collaborate on electrophysiological studies and utilize C. elegans models to further investigate our research questions, while also partnering with clinicians to translate our findings to benefit those affected.