Investigators and Program Directors

Research Interests

For many neurodegenerative diseases, including Parkinson's, Alzheimer's, and Huntington's Diseases, effective therapies are not currently available. With the advent of disease models in the fruit fly, Drosophila melanogaster, powerful genetic tools can be applied to investigate new therapeutic strategies and reveal underlying disease mechanisms. A current focus in my lab is to use the Drosophila models to determine the efficacy of "intrabody gene therapy"; a potential new therapy based on genetically engineered antibodies that are designed to recognize, bind and neutralize the pathogenic protein. We have shown that Huntington's disease pathology can be reduced significantly when antibody fragments that bind to pathogenic huntingtin protein are expressed in fly's nervous system. We are now extending our studies to Parkinson's disease models in flies, where the intrabody is directed against the presumed pathogenic protein, α-synuclein. In principle, this approach can be applied to any disorder that involves abnormal protein processing.

A related line of research in our lab is to perform genetic screens in Drosophila to determine ways to further enhance the beneficial effects of intrabody gene therapy. Finally, we are interested in teasing out the interaction between genes and environment, which is key in determining susceptibility, age of onset, and severity of human disease. Fly models, with their well-defined genetics and easily controllable environment, are excellent systems to explore the relationship between nature, nurture and the disease state.

Contact Information

E-mail: wwolfgan@wadsworth.org