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Unravel the mechanisms of synaptic and axonal degeneration in Parkinson’s disease and Lewy body dementia, and translate these discoveries to promote lifelong brain health for everyone!
Why?
Upright walking, a defining feature of humans, freed our hands and helped fuel the evolution of cognition, but it also made us vulnerable to distinctive movement disorders such as Parkinson’s disease. Importantly, Parkinson’s is not only a movement disorder; many patients also develop cognitive decline and dementia, linking it closely to Lewy body dementia.
Parkinson’s is now the world’s fastest-growing neurological disorder, affecting more than 10 million people globally and about 1.2 million people in the United States. Its prevalence rises sharply with age and is expected to increase substantially as the population grows older.
In light of its significant impact, the United States 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 and Lewy body dementia arise from a complex interplay among aging, genetic susceptibility, and environmental factors. In Parkinson’s, degeneration prominently affects dopamine-producing neurons in the nigrostriatal network, while broader synaptic and neuronal dysfunction across cortico-limbic regions contributes to cognitive decline and dementia.
Although it is well established that synapses and axons degenerate before neuronal cell bodies, the mechanisms driving this early degeneration and disease progression remain unclear.
Our lab aims to address this gap by studying Parkinson’s disease- and Lewy body dementia-associated mutations that disrupt presynaptic endolysosomal pathways. We also investigate how these mutations interact environmental risk factors, as well as aging, to drive synaptic and axonal degeneration across vulnerable brain networks.
How?
Our team is pursuing this goal through three interconnected research programs that combine mechanistic studies in mouse models, patient-derived and CRISPR-engineered iPSC neurons, cellular models, patient biospecimens, and computational analyses.
We use complementary approaches advanced techniques spanning histopathology, microscopy, biochemistry, subcellular proteomics, behavioral analysis, viral gene manipulation, bioinformatics, and cell biology to define the mechanisms driving synaptic and axonal degeneration.
Through collaborations, we also integrate electrophysiological studies and work closely with clinicians and bioinformaticians to analyze patient datasets and translate our discoveries toward improving the lives of people affected by Parkinson’s disease and Lewy body dementia.