Somshuvra Mukhopadhyay, M.B.B.S., Ph.D.

Our focus is to understand the mechanisms of, and develop treatments for, incurable human diseases. We have two major projects: **Neuroscience** **Gene-environment interactions in parkinsonism.** We seek to understand the mechanisms by which genetic mutations and environmental insults come together to cause parkinsonism, the second-most common neurodegenerative disease in the US. Our specific focus is on genes that regulate levels of essential metals (e.g. manganese, iron etc.) – these metals are necessary for normal neuronal function, but become toxic at elevated levels and induce parkinsonism. Our goals are to understand how specific gene products (e.g. transporters) regulate metal homeostasis in the brain, and how mutations in these critical genes alter brain metal homeostasis to induce parkinsonism in humans. The long-term goal is to develop small molecules that modulate brain metal levels in a manner that is effective for the treatment of parkinsonism. **Infectious Disease** **Shiga toxin-induced disease.** Shiga toxin producing *E. coli* bacteria are a major cause of lethal food-borne disease in the world. Antidotes for Shiga toxins are not available, and antibiotic treatment is contraindicated, which severely limits treatment options. The goals of this project are to determine the mechanisms by which Shiga toxins invade cells to cause disease, and design therapeutically-viable small molecule inhibitors of toxin transport for treatment.