Somshuvra (Som) Mukhopadhyay
Main Office: BME 3.510E
Alternate Office: BME 5.514
Alt. Phone: 471-5873
107 W. Dean Keeton
Austin ,TX 78712
Research SummaryParkinson's disease and parkinsonian syndromes are the second most common neuro-degenerative disease in the United States with over half a million diagnosed cases. Most parkinsonian syndromes occur due to complex interactions between genetic mutations and exposure to environmental toxicants. However, our understanding of the mechanisms by which gene-environment interactions lead to the development of parkinsonism is limited and this has impeded therapeutic progress.
Our current focus is on familial parkinsonism due to mutations in the SLC30A10 gene. In studies published over the last few years, we demonstrated that SLC30A10 is a cell surface-localized ion transporter that specifically transports the metal manganese from the cytosol to the cell exterior (i.e. mediates manganese efflux). Expression of the wild-type form of SLC30A10 reduces cellular manganese levels and protects against manganese-induced cell and neuronal death. Disease-causing mutations block the ability of the transporter to traffic to the cell surface and abolish its manganese efflux activity. Consequently, cells and neurons expressing these mutants exhibit enhanced sensitivity to manganese toxicity.
On-going efforts are designed to: 1. Develop effective treatments for manganese-induced parkinsonism, which is currently untreatable, based on enhancing manganese efflux in a therapeutically-viable manner; 2. Elucidate the mechanisms by which SLC30A10 transports manganese and regulates manganese homeostasis at the cellular and organismal level. These studies will be aided by our recent generation of SLC30A10 knock-out and knock-in mice; and 3. Understand why certain neuronal subtypes, such as those present in the globus pallidus of the basal ganglia, are specifically affected by manganese.
Please view our lab website to read more about our research, publications, and available positions.