Swetha Gowrishankar, PhD
Assistant Professor
Mentor, Biological Mechanisms
Department of Anatomy and Cell Biology
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Building & Room:
COMRB 7055
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Lab
Building & Room:
COMRB 7068
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Interrogating the molecular mechanisms underlying neuronal lysosome formation during health and disease states with a specific focus on neurodegenerative diseases
About
Lysosomes are degradative organelles, whose function is critical for protecting long-lived cells such as neurons from the build up of misfolded proteins and damaged organelles. Altered lysosome function is associated with numerous neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease and hereditary spastic paraplegia (HSP). However, the molecular mechanisms underlying their involvement are not known. My post doctoral work investigating the cell biology of amyloid plaques in AD led to the discovery of an unexpected heterogeneity of neuronal lysosomes: unlike lysosomes in neuronal cell bodies, those in neurites are deficient in luminal proteases and thus lack degradative capacity. Furthermore, I found that perturbing transport (and maturation) of the axonal pool specifically exacerbated Alzheimer's plaque pathology.
The goal of my laboratory is to now understand how these distinct lysosomal pools form, interact and function in the different parts of the neuron and how their dysfunction causes and/or exacerbates neurodegenerative diseases. Using a multidisciplinary approach (imaging, proteomics and Cas9-mediated perturbation in neurons), we will identify the defining molecular composition of these distinct lysosomal populations, factors that uniquely (or differentially) regulate them, the molecular basis for their differential responses to stresses and mechanisms underlying lysosome dysfunction in Alzheimer's disease and hereditary spastic paraplegia.