Noncoding RNAs are known to regulate gene expression at many levels via a variety of mechanisms. I have a long-term interest in studying the roles of noncoding RNAs in human neurological disorders. In my earlier work, we provided the first link between the miRNA pathway and a genetic disorder, fragile X syndrome.
I also developed a fruit fly model of fragile X-associated tremor/ataxia syndrome and provided the first evidence that RNA itself is sufficient to cause neurodegeneration. Over the last fifteen years, I have continued to study the molecular mechanisms of RNA-mediated neurodegeneration and develop potential therapeutics using both fly and mouse models.
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are heterogeneous illnesses that share a number of clinical, pathologic, and genetic features. Recently, an expanded GGGGCC (G4C2) repeat in C9ORF72 was discovered to be the most common genetic cause of ALS and FTD. We developed a Drosophila model to show that the expanded rG4C2 repeat is sufficient to cause neurodegeneration.
