Age-related neurodegeneration, including Alzheimer's Disease, Parkinson's Disease and Polyglutamine Diseases (e.g. Huntington's Disease), afflicts millions of people worldwide. Our understanding of molecular mechanisms involved in each of these diseases is incomplete, and no cures exist for them. By using a combination of in vitro biochemistry, mammalian cell biology and fruit fly (Drosophila melanogaster) genetics, the Todi laboratory is working to identify and characterize genes important for neuronal homeostasis during normal function and in disease.
A major focus of the lab’s current work centers on the physiological functions of a large class of proteases known as deubiquitinating enzymes (DUBs). DUBs are critical regulators of numerous cellular pathways, and have recently emerged as potential therapeutic targets for various diseases, including neurodegenerative ones. The Todi lab’s work with DUBs, some of which themselves cause degeneration when mutated, is shedding new light into basic cell biology and identifying novel therapeutic targets and strategies.