Huda Zoghbi's research interests grew out of her early clinical encounters with patients suffering rare and enigmatic disorders, yet her investigations into the pathogenesis of triplet repeat neurodegenerative diseases and Rett syndrome have had broad implications, not only for other more common diseases but also for our understanding of neurobiology. Conversely, the Zoghbi lab's initial foray into fundamental neurodevelopmental processes governed by Math1 has led to unexpected clinical insights.
Characterization of Pathways Mediating Neurological Phenotypes
Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and inherited ataxias, are diseases in which misfolded proteins accumulate and cause neuronal dysfunction and degeneration. Mouse genetic studies showed that decreasing the level of the culprit protein will suppress the symptoms of the disease and rescue neuronal function. Our lab has an ongoing project designed to identify new gene targets that, when inhibited, decrease mutant Ataxin-1 levels. Mutant Ataxin-1 is the protein that causes the inherited neurodegenerative disease spinocerebellar ataxia type 1. The screen to identify these targets relies on a genome-wide RNA interference (RNAi) screen. The student will participate in following up on some of the promising candidates identified through the screen to study their effects on Ataxin-1 and to establish how they might reduce protein levels. The work will involve cell culturing, RNAi, and Western analysis.
For the animal studies, the student will participate in (with the help of postdocs or graduate students) studying the behavioral features of certain mouse models of autism spectrum disorders. The student might also participate in interventional drug trials in mouse models of Rett syndrome.